Skip to main content
Download PDF
Download ePub

New insights into different adipokines in linking the pathophysiology of obesity and psoriasis

Lipids in Health and Disease volume 18, Article number: 171 (2019) Cite this article

Abstract

Psoriasis is a chronic, systemic, hyper-proliferative immune-mediated inflammatory skin disease. The results of epidemiological investigations have shown that psoriasis affects around 2% of the general population worldwide, and the total number of psoriasis patients is more than 6 million in China. Apart from the skin manifestations, psoriasis has been verified to associate with several metabolic comorbidities, such as insulin resistance, diabetes and obesity. However, the underlying mechanism is still not elucidated. Adipocytes, considered as the active endocrine cells, are dysfunctional in obesity which displays increased synthesis and secretion of adipokines with other modified metabolic properties. Currently, growing evidence has pointed to the central role of adipokines in adipose tissue and the immune system, providing new insights into the effect of adipokines in linking the pathophysiology of obesity and psoriasis. In this review, we summarize the current understanding of the pathological role of adipokines and the potential mechanisms whereby different adipokines link obesity and psoriasis. Furthermore, we also provide evidence which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases.

Introduction

Psoriasis is a chronic, systemic, hyper-proliferative, immune-mediated inflammatory skin disease. The typical psoriatic skin lesions present as silver-whitish scales with sharply demarcated, red and thickened areas [1]. The results of epidemiological surveys have shown that psoriasis affects around 2% of the general population worldwide, and the total number of psoriasis patients is more than 6 million in China [2, 3]. Obesity, defined as having a body mass index (BMI) greater than 30 kg/m2, is associated with a series of health problems that are always grouped together as metabolic syndromes [4]. Of note, obesity has nearly doubled during the past four decades all over the world [5]. In China, the prevalence of overweight was 25.8% (25.9% in males and 25.7% in females), while that of obesity was 8.1% (8.4% in males and 7.6% in females) in 2014 [6], posing serious risks to the future health and reduce the quality of life in the general population.

Presently, questions concerning the relationship of psoriasis and obesity have focused on the potential biological basis underlying the development of these two diseases. Multiple studies assume that adipokines, a type of cytokine synthesized and secreted by adipocytes, play an important role in linking the pathological process of psoriasis and obesity. As shown previously, adipocytes are the predominant cell type in adipose tissue, which are not only a passive container for storing excess energy in the form of fat [7] but also an important source of hormones and endocrine molecules, such as adipokines [8,9,10]. Under the obese status, adipocytes are enlarged and dysfunctional [11], secreting increased quantities of adipokines and exhibiting other modified metabolic properties [12]. Some adipokines, including hormones, cytokines and other proteins [13,14,15,16,17], possess pro-inflammatory properties that involve in the pathogenesis of inflammatory diseases, such as asthma [18, 19], rheumatoid arthritis (RA) [20,21,22,23] and psoriasis [12, 24, 25]. Concerning this notion, studies have demonstrated a positive relationship between psoriasis and several metabolic comorbidities, including obesity, hypertension and dyslipidemia [25, 26]. Indeed, the prevalence of obesity in psoriatic patients is higher than that in the healthy population [27], nonetheless, the underlying mechanism is still not elucidated. In this review, we summarize the current understanding of the pathological role of adipokines and the potential mechanisms whereby different adipokines link obesity and psoriasis. Furthermore, we also provide evidence which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases.

Relationship between obesity and psoriasis focusing on the prevalence rate and pathology

It has been known since the early twenty-first century that psoriasis has a greater tendency to associate with obesity and its related metabolic syndromes, a finding which has been replicated in many studies from around the world. Early in 2006, Neimann et al. have already determined a positive correlation between the increased BMI and the extent of psoriasis severity measured by the psoriasis area and severity index (PASI) score [28]. Similar result was presented by a meta-analysis in which the average prevalence of obesity in psoriasis patients was about 23.5%; concurrently, patients with high PASI scores exhibited a higher prevalence rate of obesity [29]. A systematic review including 25 studies found a higher prevalence rate of dyslipidemia in psoriasis patients with higher PASI scores [30]. The results of another comprehensive study also showed a significant relationship between PASI scores and dyslipidemia, with adjusted ORs of 1.22, 1.56, and 1.98 for mild, moderate, and severe psoriasis, respectively [31]. Since dyslipidemia is one of the hallmarks of obesity, we can infer from these results that dyslipidemia might contribute to the risk of psoriasis by promoting the pathological processes that lead to obesity. On the other hand, the incidence of psoriasis in obese children has begun to gain appreciation. Compelling evidence has demonstrated that the pediatric psoriasis is associated with a risk of pediatric metabolic syndromes [32,33,34,35], indicating an association between psoriasis and obesity in children and emphasizing the importance of careful assessment of metabolic comorbidities in psoriatic youngsters.

The association between obesity and psoriasis has also been confirmed in animal studies. Using an obese mice model with psoriasiform dermatitis induced by imiquimod (IMQ), Kanemaru et al. found that the obese status could acutely exaggerate the severity of psoriasiform dermatitis in mice. Meanwhile, the mice exhibited higher serum levels of psoriasis mediators, such as interleukin-22 (IL-22), IL-17A and its downstream molecule regenerating islet-derived 3γ (Reg3γ), which has been confirmed to be a critical molecule in psoriatic epidermal hyperplasia [36]. The results suggest that the obese status can exacerbate psoriasis-form dermatitis, at least partly, by upregulating the pro-inflammatory factors.

In summary, obesity can promote the severity of psoriasis; concurrently, psoriasis also occurs more frequently in obese people. However, the underlying mechanisms which link psoriasis with obesity has not yet been clarified. Both psoriasis and obese status could facilitate the metabolic alterations that could be the primary and triggering events [37, 38]. Nevertheless, both aberrant conditions could also develop independently because of the shared risk factors, such as genetics or lifestyles.

Adipokines are pathogenic factors which link psoriasis and obesity

Under the obese status, the pro-inflammatory adipokines are excessively synthesized and secreted by dysfunctional adipocytes. However, the anti-inflammatory adipokines are produced with a less extent. Of note, these inflammatory includes hormones, cytokines and other proteins. Given the vast array of inflammatory conditions commonly seen in obesity and psoriasis, many of which pose a great burden to the individual and society, it is important to seek a better fundamental understanding of those adipokines. Furthermore, since psoriasis and obesity always risk factors, we hypothesize that the mechanism of linking obesity and psoriasis could be explained by adipokines. A summary of the reported data about the characteristics of different adipokines in obesity and psoriasis is presented in Table 1 and Fig. 1.

Table 1 The important adipokines and the possible effects on obesity and psoriasis
Full size table
Fig. 1
figure 1

Psoriasis-signature cytokines, such as TNF-α, IL-1β and IL-6, have effects on adipose tissue being involved in key mechanisms of TG metabolism and differentiation of pre-adipocytes, including increased risk of obesity. Secreted adipokines, such as leptin, chemerin, RBP4, visfatin, fetuin-A, apelin 36 and lipocalin-2, could amplify the immune response and promote immune-mediated diseases by their pro-inflammatory effects; however, adiponectin and omentin shows anti-inflammatory effects, and the levels of adiponectin and omentin obviously decrease in obese patients. The figure briefly present the function of different adipokines in linking psoriasis and obesity

Full size image

Adiponectin

Adiponectin is exclusively synthesized by adipocytes [39], which has been shown to enhance insulin sensitivity and fatty acid oxidation. It is worth noting that adiponectin could also prevent atherosclerosis and improve anti-inflammation, playing a protective role in the pathogenesis of metabolic syndromes. In obese humans and animals, the serum levels of adiponectin are decreased and negatively correlated with the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) [40]. Additionally, adiponectin is verified to increase the production of nitric oxide (NO) in endothelial cells by activating the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) signaling pathway, thus, the lower adiponectin levels are considered to be a risk factor for endothelial dysfunction [41]. Recently, a series of studies have revealed that the adiponectin levels are reduced in patients with psoriasis and are negatively correlated with BMI [42,43,44]. In particular, the high molecular weight (HMW, oligomeric) form, one of the three major complexes of adiponectin, is confirmed as the most sensitive marker for obesity and psoriasis [45] and is significantly lower in psoriasis patients [46]. After the treatment of weight loss, the levels of adiponectin and the psoriasis-special alterations of skin have been improved to some extent [42].

Interestingly, the adiponectin also possesses anti-inflammatory properties by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway which consequently upregulates the secretion of IL-10 and regulates the toll-like receptors (TLRs) [47]. The mechanism whereby adiponectin affects obesity and psoriasis is potentially due to the regulatory role of adiponectin in skin inflammation, especially in IL-17-related psoriasis-form dermatitis. Consistent with this hypothesis, the adiponectin-deficient mice exhibit severe psoriasis-form skin inflammation with enhanced infiltration of IL-17-producing dermal Vγ4 + γδT cells, revealing that adiponectin could directly act on dermal γδ-T cells to suppress IL-17 synthesis [48]. Moreover, the synthesis and secretion of IL-17 by human CD4(+) or CD8(+) T cells are also inhibited by adiponectin [49]. With further research, the adiponectin is shown to significantly upregulate the expression level of sirtuin-1 (SIRT1) and peroxisome proliferator-activated receptor γ (PPARγ), which have a vital role in promoting the adipogenesis of adipocytes [50]. To date, the expression level of retinoid-related orphan receptor-γt (ROR-γt), one of the key transcription factors during the differentiation of Th17 cell, is synchronously inhibited by adiponectin [50]. These results have systematically uncovered the role of adiponectin in inhibiting adipogenesis of adipocytes and the Th17 cell-mediated inflammation, suggesting a novel mechanism which underlies the relationship between psoriasis and obesity.

Leptin

Leptin, a hormone that is predominately produced by adipocytes in white adipose tissue [51], has been proved as a regulator of whole-body energy homeostasis through decreasing food intake and increasing energy expenditure [52]. The plasma level of leptin is elevated in both obese and psoriatic individuals, and the elevated concentration is positively correlated with BMI and PASI scores, suggesting an important role of leptin in linking psoriasis and obesity. Indeed, several meta-analyses have evaluated the circulating concentrations of important adipokines and found that the leptin concentrations are significantly higher in non-obese patients with psoriasis [53, 54], either under the fasting or the postprandial status [55, 56], indicating that the increase leptin levels in psoriatic patients might not only originate from adipocytes but also from keratinocytes and endothelial cells [57].

Accordingly, we speculate that leptin may act as a combined bridge between psoriasis and obesity through inflammatory processes. Actually, it is worth noting that the leptin-deficient mice with IMQ-induced psoriasis presented an attenuated extent of several manifestations of inflammation, such as the clinical signs of erythema, infiltration and scales in dorsal skin and ear skin [58]; however, after the pharmacological stimulation of leptin, the authors observed that the T lymphocytes isolated from those mice are more likely to be polarized to Th1 lymphocytes with an increase secretion of several pro-inflammatory factors, including IL-6, IL-8 (CXCL8) and TNF-α [59, 60]. In addition, the proliferation of keratinocyte is also enhanced during this process. These data strongly revealed that leptin plays an important role in linking the pathogenesis of psoriasis and obesity by promoting the production of pro-inflammatory mediators.

Chemerin

Chemerin is a newly discovered adipokine which involves in the pathogenesis of inflammation, adipogenesis, angiogenesis and dyslipidemia [61]. Adipocytes, endothelial cells and skin keratinocytes have been shown to produce chemerin under the physiological status. Currently, chemerin has been considered as not only a classical chemokine but also a novel adipokine. Firstly, as a type of chemokine, chemerin mainly exhibits the chemotactic characteristics via being several cellular receptors. Previous studies have described that chemerin could bind to both the signaling and non-signaling receptors, such as G protein coupled receptor 1 (GPR1) and chemokine CC-motif receptor-like 2 (CCRL2). As known, CCRL2, which is principally expressed by keratinocytes, could promote the cellular binding capacity of chemerin and support the dendritic cells transmigration [62, 63]. On the other hand, as a vital adipokine, chemerin is shown to up-regulate in obese mammals [61, 64], and the plasma levels of chemerin are positively correlated with BMI and obesity-related biomarkers [41], pointing to a modulatory role of chemerin in the pathophysiology of obesity. Indeed, studies have demonstrated that the expression level of chemerin dramatically increases during the cellular differentiation of pre-adipocytes, and the increased chemerin could in turn stimulate the adipogenesis differentiation, leading to hyperplasia and hypertrophy of mature adipocytes [65,66,67].

Consistently, Coban et al. demonstrated a positive correlation between chemerin level with the PASI scores and BMI [68], and Gao et al. also found that the level of chemerin in psoriatic patients was higher than that in the general population [69]. Further, the adipose tissue isolated from obese and psoriatic patients is shown to secrete higher levels of chemerin [70]. After anti-psoriatic therapy, such as cyclosporine A, methotrexate and TNF-α blockers, the patients presented a relatively lower plasma levels of chemerin [71].

As mentioned above, chemerin potentially has the functions within keratinocytes and adipocytes which could induce an inflammatory response in psoriatic epidermis and adipose tissue. To validate this hypothesis, Wang et al. used the HaCaT cells and the primary human keratinocytes which were treated with chemerin previously and showed that chemerin could facilitate the secretion of inflammatory factors, including IL-1β, IL-8, TNF-α, and subsequently activate the NF-κB signaling pathway through the chemerin receptors [72]. Meanwhile, chemerin significantly reduced the expression level and constrained the deacetylase activity of SIRT1 through augmentation of reactive oxygen species (ROS) production. Similar results were observed by using the IMQ-induced psoriatic mice model [72]. Alternatively, in psoriasis dermis, chemerin is mainly secreted by fibroblasts, which could induce the migration of plasmacytoid dendritic cells (pDC) and the phosphorylation of the extracellular regulated protein kinases 1 and 2 (ERK1/2) in vitro [73]. Therefore, chemerin could act as a chemokine that recruits pDC to pre-psoriatic skin by binding to its cognate receptor, namely chemR23, expressed on pDC [74]. In conclusion, chemerin can promote NF-κB activation through inhibiting of SIRT1 activity by ROS production and consequently induce an inflammatory response, leading to the development of obesity and psoriasis.

Visfatin

Visfatin, highly expressed in visceral tissues, is a type of pro-inflammatory cytokine which could upregulate the production of pro-inflammatory factors in monocytes and then increase the activation of T lymphocytes [45]. Of note, the visfatin-knockout monocytes isolated from the arthritis mice induced by collagen exhibited a reduced secretion of IL-6 and the attenuated extent of differentiation process of CD4(+) T lymphocytes into Th17 lymphocytes [75]. Furthermore, the expression of visfatin within endothelial cells could also promote the secretion of vascular endothelial growth factors (VEGF) and synchronously lead to a decrease in the expression of metalloproteinases, which caused the proliferation of endothelial cells and the formation of capillary cavities [76].

Accumulating evidence has demonstrated that visfatin is positively correlated with abdominal obesity and is negatively correlated with the plasma level of HDL-C [77]. On the other hand, an independent study of 40 psoriatic patients showed that the plasma level of visfatin was higher than that in healthy control individuals [78]. Further research has also determined that visfatin could act on the keratinocytes and amplify the inflammatory status through NF-κB and STAT3 signaling pathways and the upregulation of several chemokines gene expression, such as CXCL8, CXCL10, CCL20 and the antimicrobial peptides including cyclic adenosine monophosphate (CAMP) and S100A7 [75, 79], thus enhancing the severity of psoriasis. This effect of visfatin has also been observed by using the IMQ-induced psoriatic mice model, in which the antimicrobial peptides were enhanced by the treatment of visfatin. Given that the antimicrobial peptides can activate the functions of pDC which may induce the development of inflammation, these observations shed light on the potential role of visfatin in linking obesity and psoriasis [80].

Omentin

Omentin has been shown to act on several different cells in mammals. For instance, in endothelial cells, omentin induces the expression and phosphorylation of nitric oxide synthase (NOS), which afterwards stimulates the vasodilation of blood vessels and the ischemia-induced tissue re-vascularization via endothelial NOS-dependent mechanisms [81]. In addition, omentin is verified to have a role in vascular smooth muscle cells which could attenuate the TNF-α-induced adhesion molecule expression and monocyte adhesion [82]. It should be further noted that apart from its protective function against insulin resistance, inflammation and vascular dysfunction, omentin is also suggested to function as a lectin which could bind to the galactofuranosyl residues that located on the cell walls of various bacteria [83, 84].

There are two isoforms of omentin in human circulation, namely omentin-1 and omentin-2. As demonstrated previously, these two isoforms are primarily produced by the omental adipose tissue and the epicardial adipose tissue but not the subcutaneous adipose tissue [85]. Of note, omentin, especially the isoform 1, is positively correlated with plasma level of adiponectin and is inversely correlated with BMI or waist-hip ratio (WHR), signifying an modulatory role in pathogenesis of obesity [86]. In a prospective study, the decreased omentin levels were shown to associate with an increased risk of obesity and insulin resistance [83]; other independent studies have further shown that serum omentin levels were clearly decreased and inversely correlated with PASI scores in psoriatic patients compared to the healthy control participants [87,88,89]. Consistently, omentin could also enhance the insulin signaling pathway and the expression of anti-inflammatory factors in adipocytes, thus suppressing the expression of different adhesion molecules induced by TNF-α [90]. To date, there are limited studies investigating omentin and its role in the pathogenesis and the clinical outcomes of psoriasis. Further studies focusing on the mechanisms whereby omentin links psoriasis and obesity are still needed.

Cytokines

As mentioned above, under the obese status, adipocytes are dysfunctional with the excessive secretion of several pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6. Given these cytokines also commonly seen in psoriasis, which pose a great burden to the development of those two diseases, it is important to seek a fundamental understanding of these cytokines. Indeed, the role of some important cytokines in the pathogenesis of disease has been investigated.

Firstly, TNF-α, as a key regulator in inflammation which is crucial for the proliferation of T lymphocytes and keratinocytes within psoriatic lesions [91], is shown to facilitate the production of pro-inflammatory cytokines by T lymphocytes and macrophages. Some researchers found that the serum levels of TNF-α increased in psoriatic patients which was also positively correlated with PASI scores [92,93,94,95]. Additionally, a positive association between TNF-α and BMI in psoriasis was demonstrated [96]. Secondly, IL-1β is another vital pro-inflammatory cytokine that promotes psoriasis and metabolic syndromes potential via the activation of keratinocytes and the inflammation-induced destruction of pancreatic β-cells, respectively [97]. Notably, several studies have found that the IL-1β level was higher in the active phase of psoriasis and reduced in psoriatic patients after treatment consequently [98, 99]; meanwhile, a positive correlation between the serum levels of IL-1β with PASI has also been reported in psoriatic patients before and after treatment [100,101,102], signifying that IL-1β is an important mediator in the initiation and maintenance of psoriatic plaques. Thirdly, similar to IL-1β, IL-6 could clearly impair the insulin release and induce the production of inflammatory cytokines in adipocytes [97]. Moreover, IL-6 also mediates the activation of T lymphocytes and the proliferation of keratinocytes [102]. Current results have revealed that IL-6 is increased under the psoriatic status and positively correlates with PASI scores, at least in the more severe form of psoriasis [103, 104].

In conclusion, TNF-α, IL-6 and IL-1β are increased in psoriasis and correlate with PASI scores and obesity, leading to worsening of psoriatic lesions. The increasing results of functional analyses focusing on the cytokines could point out the potential mechanisms by which cytokines may increase susceptibility to obesity and psoriasis. However, there are also multiple cytokines which aberrantly produced under the diseases status, further studies is still needed to shed light on the physiological role of the other cytokines in linking obesity and psoriasis.

Other important adipokines

Several other important adipokines have recently been considered as mediators of obesity and psoriasis, although there is a lack of experimental evidence that directly supports specific mechanisms. These adipokines include retinol binding protein 4 (RBP4), fetuin-A (FetA) and lipocalin-2 (LCN2).

RBP4

RBP4, an adipokine which predominantly secreted by adipocytes, macrophages and hepatocytes, was first discovered in 2005 [105, 106]. Especially, RBP4 is produced by the visceral adipocytes under the status of obesity and insulin resistance. It has been known since the early twenty-first century that RBP4 has a greater tendency to involve in several metabolic processes in humans and mice, a finding which has been replicated in many studies from around the world. Currently, the role of RBP4 in linking obesity and psoriasis has been given substantial attention.

Accordingly, accumulating evidence has revealed that increased RBP4 levels are positively associated with BMI, WHR, plasma level of TG and systolic blood pressure. By contrast, the serum levels of RBP4 are shown to inversely associate with plasma HDL-C levels, pointing out that RBP4 has an essential role in promoting the pathological process of obesity [107,108,109]. Furthermore, in psoriasis patients with obesity, the plasma levels of RBP4 are positively correlated with the PASI score and higher than those in patients with simple psoriasis [110,111,112]. Further research has also determined that RBP4 is positively associated with the circulating levels of inflammatory factors, such as IL-6 and TNF-α [112]. Of note, treatment with acitretin could significantly reduce the plasma levels RBP4 in psoriasis patients [113], suggesting that RBP4 is a potential target for treatment of psoriasis.

FetA

FetA, encoded by FETA genes, is produced by adipocytes, keratinocytes and hepatocytes, especially those isolated from mice or human donors with obesity and metabolic syndromes [114, 115]. Growing evidence reveals that the free fatty acids (FFA) could enhance the production of FetA in hepatocytes and adipocytes via increasing the activation NF-κB signaling pathway. Furthermore, the serum levels of FetA significantly reduce after the treatment of weight loss in obese patients, indicating consequently that FetA is associated with obesity [116].

On the other hand, the role of FetA in the pathogenesis of inflammation, both in the systemic and tissue-specific inflammation, has received substantial attention in recent years. As described previously, FetA could induce the synthesis and secretion of pro-inflammatory adipokines and synergistically inhibit the lipid efflux especially within macrophages [117, 118]. In addition, the adipocyte-derived FetA shows the effect on the transformation of the anti-inflammatory M2-phenotype macrophages into the pro-inflammatory M1-phenotype macrophages, thus promoting the inflammatory process in humans [116]. These results suggest a potential mechanism by which FetA influences the process of inflammation. Given that psoriasis is a chronic systemic inflammatory disease, we could make a reasonable speculation that FetA could also have a role in the pathogenesis of psoriasis. Nonetheless, few studies have reported the relationship between FetA levels and psoriasis. It is worth noting that Genc et al. found that the FetA levels in psoriatic patients was higher than those in healthy individuals, suggesting that FetA may have a role in psoriasis pathogenesis [119]. Likewise, Uyar et al. also found that serum levels of FetA in psoriatic patients was positively correlated with PASI scores.

However, due to the lack of evidence supporting a direct mechanism whereby FetA affect psoriasis, further efforts should be made to elucidate the important role of FetA in promoting obesity and psoriasis.

LCN2

More recently, another adipokine named LCN2 has attracted broad attention. LCN2, expressed in human livers, lungs, kidneys and adipose tissues [120], is a 25 kDa glycoprotein member of the highly heterogeneous family of lipocalins. Previous studies have demonstrated that LCN-2 is a component of the innate immune system with a relevant role in the acute phase response to infection as well in as the induction of apoptosis; concurrently, LCN2 is also shown to involve in several inflammatory diseases, including the epidermal inflammation, the inflammatory bowel disease (IBD) and atherosclerotic diseases.

For instance, Baran et al. found that the serum levels of LCN2 were significantly increased in psoriatic patients compared to the healthy controls [110], and two other independent studies have revealed that the serum levels of LCN2 in psoriaeic patients correlated with PASI scores [112, 121]. Likewise, in an animal study, Hau et al. found that the erythema and scaling skin isolated from IMQ-induced psoriatic mice presented higher expression level of LCN2 gene, suggesting that LCN2 plays an important role in promoting the development of psoriasis [75]. Interestingly, these findings have been replicated in other studies from around the world. Wolk et al. and Hadidi et al. provided the evidence that LCN2 is significantly up-regulated in keratinocytes of psoriatic skin lesions, and the LCN2 level is positively correlated with IL-1β [88, 122], while IL-1β promotes obesity and psoriasis synergistically, thus emphasizing the regulatory nature of LCN2 in linking psoriasis and obesity.

Treatment of obesity and psoriasis through targeting adipokines

Several studies have shown that the treatment of weight loss in obese patients may effectively improve the pathogenesis of psoriasis. Alternatively, the effects of diet control or exercise in obese patients with moderate-to-severe psoriasis also revealed that the mean weight of these patients was significantly lower in the diet-controlling group compared to that in the control group. In addition, around 66.7% of the obese patients in the diet-controlling group achieved about 75% decrease in their PASI score (PASI-75), and the percentage of patients who achieved PASI-75 was only around 29% in the control group. Mechanically, the authors also found that a low-calorie diet could further reduce the serum level of leptin and simultaneously increased the serum level of adiponectin [123, 124], indicating that lifestyle modifications may be the supplements in addition to the pharmacologic treatment of obese patients with psoriasis.

On the other hand, several studies have already pointed to the regulation of the concentration of adipokines and have demonstrated that the treatment of weight loss in obese patients with psoriasis should focus more on reducing obesity-induced inflammation and adipokine secretion. More recently, studies have signified that the psoriatic patients treated with the fumaric acid esters or methotrexate had an increased serum level of adiponectin compared to that in patients per se before treatment [125,126,127]. In addition, the psoriatic patients treated with anti-TNFα agents also had a significantly increase in the serum level of adiponectin and a reduction in the serum level of IL-6, suggesting that aiming at adipokines might help to treat psoriasis and obesity [128]. Nevertheless, we still need more large-scale prospective studies in patients to determine the validity of the values about the treating effect.

Conclusions and perspectives

In summary, there is a complex relationship between obesity, psoriasis and adipokines. According to the results of studies, psoriasis and obesity may not be reciprocally causal but may be derived from a shared pathophysiology. To this point, future studies focusing on the relationship are important, not only from the public health perspective but also to achieve more comprehensive management of psoriasis. Before a decision is made about which the therapeutic intervention should be applied to managing a psoriatic patient, it seems important to consider synchronously that the body weight of the patients is also involved in the management. Psoriatic patients may be evaluated from both a dermatological and a metabolic perspective.

Currently, the PASI is being used to evaluate the severity of psoriasis and the affected body areas; meanwhile, the evaluation of bodyweight would also be valuable and would complement the clinical assessment of the psoriatic patients. The complex interaction of psoriasis with different comorbidities suggests the need for a multidisciplinary approach in the management of obese patients with psoriasis.

Further research is required to elucidate the role of adipokines in patients with psoriasis and psoriasis-related comorbidities. The assessment of the serum levels of adipokines in a well-phenotyped population with psoriasis, while controlling for endocrine factors, is important for further understanding the disease. Adipokines may be mediators of cutaneous inflammation, which suggests a role in the pathogenesis of psoriasis and the development of obesity.

Availability of data and materials

Not applicable.

Abbreviations

BMI:

Body mass index

CAMP:

Cyclic adenosine monophosphate

CCRL2:

Chemokine CC-motif receptor-like 2

ERK1/2:

Extracellular regulated protein kinases 1 and 2

FetA:

Fetuin-A

FFA:

Free fatty acids

GPR1G:

Protein coupled receptor 1

HMW:

High molecular weight

IBD:

Inflammatory bowel disease

IL-6:

Interleukin-6

LCN2:

Lipocalin-2

NF-κB:

Nuclear factor kappa B

NO:

Nitric oxide

NOS:

Nitric oxide synthase

PASI:

Psoriasis area and severity index

pDC:

Plasmacytoid dendritic cells

PI3K:

Phosphatidylinositol-3 kinase

PPARγ:

Peroxisome proliferator-activated receptor gamma

RA:

Rheumatoid arthritis

RBP4:

Retinol binding protein 4

Reg3γ:

Regenerating islet-derived 3-gamma

ROR-γt:

Retinoid-related orphan receptor-gamma-t

ROS:

Reactive oxygen species

SIRT1:

Sirtuin-1

TLRs:

Toll-like receptors

TNF-α:

Tumor necrosis factor-alpha

VEGF:

Vascular endothelial growth factors

WHR:

Waist-hip ratio

References

  1. Wenk KS, Arrington KC, Ehrlich A. Psoriasis and non-alcoholic fatty liver disease. J Eur Acad Dermatol Venereol. 2011;25:383–91.

    Article  CAS  PubMed  Google Scholar 

  2. Zhang L, Yang H, Wang Y, Chen Y, Zhou H, Shen Z. Self-medication of psoriasis in southwestern China. Dermatology. 2014;228:368–74.

    Article  PubMed  Google Scholar 

  3. Ding X, Wang T, Shen Y, Wang X, Zhou C, Tian S, Liu Y, Peng G, Zhou J, Xue S, et al. Prevalence of psoriasis in China: a population-based study in six cities. Eur J Dermatol. 2012;22:663–7.

    PubMed  Google Scholar 

  4. Zheng XY, Zhao SP, Yu BL, Wu CL, Liu L. Apolipoprotein A5 internalized by human adipocytes modulates cellular triglyceride content. Biol Chem. 2012;393:161–7.

    Article  CAS  PubMed  Google Scholar 

  5. Collaboration NCDRF. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387:1377–96.

    Article  Google Scholar 

  6. Zhang Q, Yang YJ, Wang H, Li N, Wang TJ, Qian HY, Jin C. Atorvastatin treatment improves the effects of mesenchymal stem cells transplantation on acute myocardial infarction: the role of Rhoa/rock/Erk pathway. J Am Coll Cardiol. 2014;63:A187.

    Article  Google Scholar 

  7. Engin A. The Pathogenesis of Obesity-Associated Adipose Tissue Inflammation. Adv Exp Med Biol. 2017;960:221–45.

  8. Hassan M, El Yazidi C, Landrier JF, Lairon D, Margotat A, Amiot MJ. Phloretin enhances adipocyte differentiation and adiponectin expression in 3T3-L1 cells. Biochem Biophys Res Commun. 2007;361:208–13.

    Article  CAS  PubMed  Google Scholar 

  9. Puri V, Czech MP. Lipid droplets: FSP27 knockout enhances their sizzle. J Clin Invest. 2008;118:2693–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Ryden M, Andersson DP, Bernard S, Spalding K, Arner P. Adipocyte triglyceride turnover and lipolysis in lean and overweight subjects. J Lipid Res. 2013;54:2909–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tang QQ, Lane MD. Adipogenesis: from stem cell to adipocyte. Annu Rev Biochem. 2012;81:715–36.

    Article  CAS  PubMed  Google Scholar 

  12. Kralisch S, Fasshauer M. Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease? Diabetologia. 2013;56:10–21.

    Article  CAS  PubMed  Google Scholar 

  13. Kumar A, Nayak BP, Kumar A. Obesity: single house for many evils. Minerva Endocrinol. 2016;41:499–508.

    PubMed  Google Scholar 

  14. Katsiki N, Mantzoros C, Mikhailidis DP. Adiponectin, lipids and atherosclerosis. Curr Opin Lipidol. 2017;28:347–54.

    Article  CAS  PubMed  Google Scholar 

  15. Georgiou GP, Provatopoulou X, Kalogera E, Siasos G, Menenakos E, Zografos GC, Gounaris A. Serum resistin is inversely related to breast cancer risk in premenopausal women. Breast. 2016;29:163–9.

    Article  PubMed  Google Scholar 

  16. Bastien M, Poirier P, Lemieux I, Despres JP. Overview of epidemiology and contribution of obesity to cardiovascular disease. Prog Cardiovasc Dis. 2014;56:369–81.

    Article  PubMed  Google Scholar 

  17. Adolph TE, Grander C, Grabherr F, Tilg H. Adipokines and non-alcoholic fatty liver disease: multiple interactions. Int J Mol Sci. 2017;18:E1649.

    Article  PubMed  CAS  Google Scholar 

  18. Sideleva O, Suratt BT, Black KE, Tharp WG, Pratley RE, Forgione P, Dienz O, Irvin CG, Dixon AE. Obesity and asthma an inflammatory disease of adipose tissue not the airway. Am J Respir Crit Care Med. 2012;186:598–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Muc M, Todo-Bom A, Mota-Pinto A, Vale-Pereira S, Loureiro C. Leptin and resistin in overweight patients with and without asthma. Allergol Immunopathol. 2014;42:415–21.

    Article  CAS  Google Scholar 

  20. Yoshino T, Kusunoki N, Tanaka N, Kaneko K, Kusunoki Y, Endo H, Hasunuma T, Kawai S. Elevated serum levels of Resistin, leptin, and adiponectin are associated with C-reactive protein and also other clinical conditions in rheumatoid arthritis. Intern Med. 2011;50:269–75.

    Article  CAS  PubMed  Google Scholar 

  21. Waluga M, Hartleb M, Boryczka G, Kukla M, Zwirska-Korczala K. Serum adipokines in inflammatory bowel disease. World J Gastroenterol. 2014;20:6912–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Konrad A, Lehrke M, Schachinger V, Seibold F, Stark R, Ochsenkuhn T, Parhofer KG, Goke B, Broedl UC. Resistin is an inflammatory marker of inflammatory bowel disease in humans. Eur J Gastroenterol Hepatol. 2007;19:1070–4.

    Article  CAS  PubMed  Google Scholar 

  23. Garrido JADB, Magana MS. Leptin and rheumatoid arthritis, influence of this adipokine in the disease. Revista Cubana De Reumatologia. 2016;18:129–41.

    Google Scholar 

  24. Torres S, Fabersani E, Marquez A, Gauffin-Cano P. Adipose tissue inflammation and metabolic syndrome. The proactive role of probiotics. Eur J Nutr. 2019;58:27–43.

    Article  PubMed  Google Scholar 

  25. Shipman AR, Millington GW. Obesity and the skin. Br J Dermatol. 2011;165:743–50.

    Article  CAS  PubMed  Google Scholar 

  26. Dauden E, Blasco AJ, Bonanad C, Botella R, Carrascosa JM, Gonzalez-Parra E, Jodar E, Joven B, Lazaro P, Olveira A, et al. Position statement for the Management of Comorbidities in psoriasis. J Eur Acad Dermatol Venereol. 2018;32(12):2058–73.

    Article  CAS  PubMed  Google Scholar 

  27. Cooksey R, Brophy S, Kennedy J, Gutierrez FF, Pickles T, Davies R, Piguet V, Choy E. Cardiovascular risk factors predicting cardiac events are different in patients with rheumatoid arthritis, psoriatic arthritis, and psoriasis. Semin Arthritis Rheum. 2018;48(3):367–73.

    Article  PubMed  Google Scholar 

  28. Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB, Gelfand JM. Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol. 2006;55:829–35.

    Article  PubMed  Google Scholar 

  29. Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies. Nutr Diabetes. 2012;2:e54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Miller IM, Ellervik C, Yazdanyar S, Jemec GBE. Meta-analysis of psoriasis, cardiovascular disease, and associated risk factors. J Am Acad Dermatol. 2013;69:1014–24.

    Article  PubMed  Google Scholar 

  31. Upala S, Sanguankeo A. Effect of lifestyle weight loss intervention on disease severity in patients with psoriasis: a systematic review and meta-analysis. Int J Obes. 2015;39:1197–202.

    Article  CAS  Google Scholar 

  32. Kimball AB, Alavian C, Alora-Palli M, Bagel J. Weight loss in obese patients with psoriasis can be successfully achieved during a course of phototherapy. J Eur Acad Dermatol Venereol. 2012;26:1582–4.

    CAS  PubMed  Google Scholar 

  33. Augustin M, Glaeske G, Radtke MA, Christophers E, Reich K, Schafer I. Epidemiology and comorbidity of psoriasis in children. Br J Dermatol. 2010;162:633–6.

    Article  CAS  PubMed  Google Scholar 

  34. Hunjan MK, Maradit Kremers H, Lohse C, Tollefson M. Association between obesity and pediatric psoriasis. Pediatr Dermatol. 2018;35(5):e304–5.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Guidolin L, Borin M, Fontana E, Caroppo F, Piaserico S, Fortina AB. Central obesity in children with psoriasis. Acta Derm Venereol. 2018;98:282–3.

    Article  PubMed  Google Scholar 

  36. Kanemaru K, Matsuyuki A, Nakamura Y, Fukami K. Obesity exacerbates imiquimod-induced psoriasis-like epidermal hyperplasia and interleukin-17 and interleukin-22 production in mice. Exp Dermatol. 2015;24:436–42.

    Article  CAS  PubMed  Google Scholar 

  37. Chu TW, Tsai TF. Psoriasis and cardiovascular comorbidities with emphasis in Asia. G Ital Dermatol Venereol. 2012;147:189–202.

    CAS  PubMed  Google Scholar 

  38. Baran A, Flisiak I, Jaroszewicz J, Swiderska M. Serum adiponectin and leptin levels in psoriatic patients according to topical treatment. J Dermatolog Treat. 2015;26:134–8.

    Article  CAS  PubMed  Google Scholar 

  39. Jensen P, Skov L. Psoriasis and obesity. Dermatology. 2016;232:633–9.

    Article  PubMed  Google Scholar 

  40. Sereflican B, Goksugur N, Bugdayci G, Polat M, Parlak AH. Serum Visfatin, adiponectin, and tumor necrosis factor alpha (TNF-alpha) levels in patients with psoriasis and their correlation with disease severity. Acta Dermatovenerol Croat. 2016;24:13–9.

    CAS  PubMed  Google Scholar 

  41. Ferland DJ, Watts SW. Chemerin: a comprehensive review elucidating the need for cardiovascular research. Pharmacol Res. 2015;99:351–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Coimbra S, Oliveira H, Reis F, Belo L, Rocha S, Quintanilha A, Figueiredo A, Teixeira F, Castro E, Rocha-Pereira P, Santos-Silva A. Circulating levels of adiponectin, oxidized LDL and C-reactive protein in Portuguese patients with psoriasis vulgaris, according to body mass index, severity and duration of the disease. J Dermatol Sci. 2009;55:202–4.

    Article  CAS  PubMed  Google Scholar 

  43. Oh YJ, Lim HK, Choi JH, Lee JW, Kim NI. Serum leptin and adiponectin levels in Korean patients with psoriasis. J Korean Med Sci. 2014;29:729–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Warnecke C, Manousaridis I, Herr R, Terris DD, Goebeler M, Goerdt S, Peitsch WK. Cardiovascular and metabolic risk profile in German patients with moderate and severe psoriasis: a case control study. Eur J Dermatol. 2011;21:761–70.

    PubMed  Google Scholar 

  45. Gerdes S, Osadtschy S, Rostami-Yazdi M, Buhles N, Weichenthal M, Mrowietz U. Leptin, adiponectin, visfatin and retinol-binding protein-4 - mediators of comorbidities in patients with psoriasis? Exp Dermatol. 2012;21:43–7.

    Article  CAS  PubMed  Google Scholar 

  46. Nakajima H, Nakajima K, Tarutani M, Morishige R, Sano S. Kinetics of circulating Th17 cytokines and adipokines in psoriasis patients. Arch Dermatol Res. 2011;303:451–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wang X, Chen Q, Pu H, Wei Q, Duan M, Zhang C, Jiang T, Shou X, Zhang J, Yang Y. Adiponectin improves NF-kappaB-mediated inflammation and abates atherosclerosis progression in apolipoprotein E-deficient mice. Lipids Health Dis. 2016;15:33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Shibata S, Tada Y, Hau CS, Mitsui A, Kamata M, Asano Y, Sugaya M, Kadono T, Masamoto Y, Kurokawa M, et al. Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from gamma delta-T cells. Nat Commun. 2015;6:7687.

  49. Kim JW, Lee YS, Seol DJ, Cho IJ, Ku SK, Choi JS, Lee HJ. Anti-obesity and fatty liver-preventing activities of Lonicera caerulea in high-fat diet-fed mice. Int J Mol Med. 2018;42:3047–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Wicinski M, Malinowski B, Weclewicz MM, Grzesk E, Grzesk G. Anti-atherogenic properties of resveratrol: 4-week resveratrol administration associated with serum concentrations of SIRT1, adiponectin, S100A8/A9 and VSMCs contractility in a rat model. Exp Ther Med. 2017;13:2071–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Robati RM, Partovi-Kia M, Haghighatkhah HR, Younespour S, Abdollahimajd F. Increased serum leptin and resistin levels and increased carotid intima-media wall thickness in patients with psoriasis: is psoriasis associated with atherosclerosis? J Am Acad Dermatol. 2014;71:642–8.

    Article  CAS  PubMed  Google Scholar 

  52. Zhu KJ, Shi G, Zhang C, Li M, Zhu CY, Fan YM. Adiponectin levels in patients with psoriasis: a meta-analysis. J Dermatol. 2013;40:438–42.

    Article  CAS  PubMed  Google Scholar 

  53. Kyriakou A, Patsatsi A, Sotiriadis D, Goulis DG. Serum leptin, Resistin, and adiponectin concentrations in psoriasis: a meta-analysis of observational studies. Dermatology. 2017;233:378–89.

    Article  CAS  PubMed  Google Scholar 

  54. Johnston A, Arnadottir S, Gudjonsson JE, Aphale A, Sigmarsdottir AA, Gunnarsson SI, Steinsson JT, Elder JT, Valdimarsson H. Obesity in psoriasis: leptin and resistin as mediators of cutaneous inflammation. Br J Dermatol. 2008;159:342–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hamminga EA, van der Lely AJ, Neumann HA, Thio HB. Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypotheses. 2006;67:768–73.

    Article  CAS  PubMed  Google Scholar 

  56. Aly DG, Abdallah IY, Hanafy NS, Elsaie ML, Hafiz NA. Elevated serum leptin levels in nonobese patients with psoriasis. J Drugs Dermatol. 2013;12:e25–9.

    PubMed  Google Scholar 

  57. Poeggeler B, Schulz C, Pappolla MA, Bodo E, Tiede S, Lehnert H, Paus R. Leptin and the skin: a new frontier. Exp Dermatol. 2010;19:12–8.

    Article  CAS  PubMed  Google Scholar 

  58. Stjernholm T, Ommen P, Langkilde A, Johansen C, Iversen L, Rosada C, Stenderup K. Leptin deficiency in mice counteracts imiquimod (IMQ)-induced psoriasis-like skin inflammation while leptin stimulation induces inflammation in human keratinocytes. Exp Dermatol. 2017;26:338–45.

    Article  CAS  PubMed  Google Scholar 

  59. Xue K, Liu H, Jian Q, Liu B, Zhu D, Zhang M, Gao L, Li C. Leptin induces secretion of pro-inflammatory cytokines by human keratinocytes in vitro--a possible reason for increased severity of psoriasis in patients with a high body mass index. Exp Dermatol. 2013;22:406–10.

    Article  CAS  PubMed  Google Scholar 

  60. Lee M, Lee E, Jin SH, Ahn S, Kim SO, Kim J, Choi D, Lim KM, Lee ST, Noh M. Leptin regulates the pro-inflammatory response in human epidermal keratinocytes. Arch Dermatol Res. 2018;310:351–62.

    Article  CAS  PubMed  Google Scholar 

  61. Helfer G, Wu QF. Chemerin: a multifaceted adipokine involved in metabolic disorders. J Endocrinol. 2018;238:R79–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bai Y, Sun Q. Macrophage recruitment in obese adipose tissue. Obes Rev. 2015;16:127–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Rourke JL, Muruganandan S, Dranse HJ, McMullen NM, Sinal CJ. Gpr1 is an active chemerin receptor influencing glucose homeostasis in obese mice. J Endocrinol. 2014;222:201–15.

    Article  CAS  PubMed  Google Scholar 

  64. Gateva A, Assyov Y, Tsakova A, Kamenov Z. Classical (adiponectin, leptin, resistin) and new (chemerin, vaspin, omentin) adipocytokines in patients with prediabetes. Horm Mol Biol Clin Invest. 2018;34.

  65. Zylla S, Pietzner M, Kuhn JP, Volzke H, Dorr M, Nauck M, Friedrich N. Serum Chemerin is associated with inflammatory and metabolic parameters-results of a population-based study. Obesity. 2017;25:468–75.

    Article  CAS  PubMed  Google Scholar 

  66. Watts SW, Dorrance AM, Penfold ME, Rourke JL, Sinal CJ, Seitz B, Sullivan TJ, Charvat TT, Thompson JM, Burnett R, Fink GD. Chemerin Connects Fat to Arterial Contraction. Arterioscler Thromb Vasc Biol. 2013;33:1320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hansen D, Dendale P, Beelen M, Jonkers RAM, Mullens A, Corluy L, Meeusen R, van Loon LJC. Plasma adipokine and inflammatory marker concentrations are altered in obese, as opposed to non-obese, type 2 diabetes patients. Eur J Appl Physiol. 2010;109:397–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Coban M, Tasli L, Turgut S, Ozkan S, Ata MT, Akin F. Association of Adipokines, insulin resistance, hypertension and dyslipidemia in patients with psoriasis vulgaris. Ann Dermatol. 2016;28:74–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gao XY, Mi SH, Zhang FZ, Gong FY, Lai YQ, Gao F, Zhang XX, Wang LJ, Tao H. Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis. Cardiovasc Diabetol. 2011;10:87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Motawi TMK, Mahdy SG, El-Sawalhi MM, Ali EN, El-Telbany RFA. Serum levels of chemerin, apelin, vaspin, and omentin-1 in obese type 2 diabetic Egyptian patients with coronary artery stenosis. Can J Physiol Pharmacol. 2018;96:38–44.

    Article  CAS  PubMed  Google Scholar 

  71. Malin SK, Navaneethan SD, Mulya A, Huang H, Kirwan JP. Exercise-induced lowering of chemerin is associated with reduced cardiometabolic risk and glucose-stimulated insulin secretion in older adults. J Nutr Health Aging. 2014;18:608–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wang Y, Huo J, Zhang D, Hu G, Zhang Y. Chemerin/ChemR23 axis triggers an inflammatory response in keratinocytes through ROS-sirt1-NF-kappaB signaling. J Cell Biochem. 2019;120:6459–70.

    Article  CAS  PubMed  Google Scholar 

  73. Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S, Villanueva EC, Shah P, Kaplan MJ, Bruce AT. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187:490–500.

    Article  CAS  PubMed  Google Scholar 

  74. Albanesi C, Scarponi C, Pallotta S, Daniele R, Bosisio D, Madonna S, Fortugno P, Gonzalvo-Feo S, Franssen JD, Parmentier M, et al. Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment. J Exp Med. 2009;206:249–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Hau CS, Kanda N, Noda S, Tatsuta A, Kamata M, Shibata S, Asano Y, Sato S, Watanabe S, Tada Y. Visfatin enhances the production of cathelicidin antimicrobial peptide, human beta-Defensin-2, human beta-Defensin-3, and S100A7 in human keratinocytes and their Orthologs in murine Imiquimod-induced psoriatic skin. Am J Pathol. 2013;182:1705–17.

    Article  CAS  PubMed  Google Scholar 

  76. Chiricozzi A, Raimondo A, Lembo S, Fausti F, Dini V, Costanzo A, Monfrecola G, Balato N, Ayala F, Romanelli M, Balato A. Crosstalk between skin inflammation and adipose tissue-derived products: pathogenic evidence linking psoriasis to increased adiposity. Expert Rev Clin Immunol. 2016;12:1299–308.

    Article  CAS  PubMed  Google Scholar 

  77. Siahanidou T, Margeli A, Kappis A, Papassotiriou I, Mandyla H. Circulating visfatin levels in healthy preterm infants are independently associated with high-density lipoprotein cholesterol levels and dietary long-chain polyunsaturated fatty acids. Metab Clin Exp. 2011;60:389–93.

    Article  CAS  PubMed  Google Scholar 

  78. Imai A, Satoi K, Fujimoto E, Sato K. Inducing maternal inflammation promotes leptin production in offspring but does not improve allergic symptoms in a mouse model of allergic rhinitis. Heliyon. 2017;3:e00327.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Kanda N, Hau CS, Tada Y, Tatsuta A, Sato S, Watanabe S. Visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes. Endocrinology. 2011;152:3155–64.

    Article  CAS  PubMed  Google Scholar 

  80. Morizane S, Yamasaki K, Muhleisen B, Kotol PF, Murakami M, Aoyama Y, Iwatsuki K, Hata T, Gallo RL. Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands. J Invest Dermatol. 2012;132:135–43.

    Article  CAS  PubMed  Google Scholar 

  81. Saddic LA, Nicoloro SM, Gupta OT, Czech MP, Gorham J, Shernan SK, Seidman CE, Seidman JG, Aranki SF, Body SC, et al. Joint analysis of left ventricular expression and circulating plasma levels of Omentin after myocardial ischemia. Cardiovasc Diabetol. 2017;16:87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Alizadeh M, Asad MR, Faramarzi M, Afroundeh R. Effect of eight-week high intensity interval training on Omentin-1 gene expression and insulin-resistance in diabetic male rats. Ann Appl Sport Sci. 2017;5:29–36.

    Article  Google Scholar 

  83. Du Y, Ji Q, Cai L, Huang F, Lai Y, Liu Y, Yu J, Han B, Zhu E, Zhang J, et al. Association between omentin-1 expression in human epicardial adipose tissue and coronary atherosclerosis. Cardiovasc Diabetol. 2016;15:90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Bozkurt Dogan S, Ongoz Dede F, Balli U, Sertoglu E. Levels of vaspin and omentin-1 in gingival crevicular fluid as potential markers of inflammation in patients with chronic periodontitis and type 2 diabetes mellitus. J Oral Sci. 2016;58:379–89.

    Article  PubMed  CAS  Google Scholar 

  85. Ismail SA, Mohamed SA. Serum levels of visfatin and omentin-1 in patients with psoriasis and their relation to disease severity. Br J Dermatol. 2012;167:436–9.

    Article  CAS  PubMed  Google Scholar 

  86. Kort DH, Kostolias A, Sullivan C, Lobo RA. Chemerin as a marker of body fat and insulin resistance in women with polycystic ovary syndrome. Gynecol Endocrinol. 2015;31:152–5.

    Article  CAS  PubMed  Google Scholar 

  87. Zhang C, Zhu KJ, Liu JL, Xu GX, Liu W, Jiang FX, Zheng HF, Quan C. Omentin-1 plasma levels and omentin-1 expression are decreased in psoriatic lesions of psoriasis patients. Arch Dermatol Res. 2015;307:455–9.

    Article  CAS  PubMed  Google Scholar 

  88. Wolk K, Sabat R. Adipokines in psoriasis: an important link between skin inflammation and metabolic alterations. Rev Endocr Metab Disord. 2016;17:305–17.

    Article  CAS  PubMed  Google Scholar 

  89. Takahashi H, Tsuji H, Honma M, Ishida-Yamamoto A, Iizuka H. Increased plasma resistin and decreased omentin levels in Japanese patients with psoriasis. Arch Dermatol Res. 2013;305:113–6.

    Article  CAS  PubMed  Google Scholar 

  90. Watanabe T, Watanabe-Kominato K, Takahashi Y, Kojima M, Watanabe R. Adipose tissue-derived Omentin-1 function and regulation. Compr Physiol. 2017;7:765–81.

    Article  PubMed  Google Scholar 

  91. Digre A, Singh K, Abrink M, Reijmers RM, Sandler S, Vlodavsky I, Li JP. Overexpression of heparanase enhances T lymphocyte activities and intensifies the inflammatory response in a model of murine rheumatoid arthritis. Sci Rep. 2017;7:46229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Liu PP, He YJ, Wang HL, Kuang YH, Chen WQ, Li J, Chen ML, Zhang JL, Su J, Zhao S, et al. The expression of mCTLA-4 in skin lesion inversely correlates with the severity of psoriasis. J Dermatol Sci. 2018;89:233–40.

    Article  CAS  PubMed  Google Scholar 

  93. Kaur S, Zilmer K, Leping V, Zilmer M. Comparative study of systemic inflammatory responses in psoriasis vulgaris and mild to moderate allergic contact dermatitis. Dermatology. 2012;225:54–61.

    Article  CAS  PubMed  Google Scholar 

  94. Corbetta S, Angioni R, Cattaneo A, Beck-Peccoz P, Spada A. Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines. Eur J Endocrinol. 2006;154:83–6.

    Article  CAS  PubMed  Google Scholar 

  95. Abanmi A, Al Harthi F, Khan HA, Tariq M. Serum levels of proinflammatory cytokines in psoriasis patients from Saudi Arabia. Int J Dermatol. 2005;44:82–3.

    Article  PubMed  Google Scholar 

  96. Takahashi H, Tsuji H, Ishida-Yamamoto A, Iizuka H. Serum level of adiponectin increases and those of leptin and resistin decrease following the treatment of psoriasis. J Dermatol. 2013;40:475–6.

    Article  PubMed  Google Scholar 

  97. Elkayam O, Yaron I, Shirazi I, Yaron M, Caspi D. Serum levels of IL-10, IL-6, IL-1ra, and sIL-2R in patients with psoriatic arthritis. Rheumatol Int. 2000;19:101–5.

    Article  CAS  PubMed  Google Scholar 

  98. Wilms H, Sievers J, Rickert U, Rostami-Yazdi M, Mrowietz U, Lucius R. Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1 beta, TNF-alpha and IL-6 in an in-vitro model of brain inflammation. J Neuroinflammation. 2010;7.

  99. Vijayalakshmi A, Ravichandiran V, Masilamani K. Antipsoriatic and inhibitory effects of an oral dosage form containing bioflavonoids on inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-17 and TNF-alpha. Indian J Pharm Edu Res. 2014;48:139–48.

    Google Scholar 

  100. Nakajima A, Matsuki T, Komine M, Asahina A, Horai R, Nakae S, Ishigame H, Kakuta S, Saijo S, Iwakura Y. TNF, but not IL-6 and IL-17, is crucial for the development of T cell-independent psoriasis-like dermatitis in Il1rn(−/−) mice. J Immunol. 2010;185:1887–93.

    Article  CAS  PubMed  Google Scholar 

  101. Krupkova M, Janku M, Liska F, Sedova L, Kazdova L, Krenova D, Kren V, Seda O. Pharmacogenetic model of retinoic acid-induced dyslipidemia and insulin resistance. Pharmacogenomics. 2009;10:1915–27.

    Article  CAS  PubMed  Google Scholar 

  102. Andre LGS, Correia-Silva JDF, Diniz MG, Xavier GM, Horta MCR, Gomez RS. Investigation of functional gene polymorphisms: IL-1B, IL-6 and TNFA in benign migratory glossitis in Brazilian individuals. J Oral Pathol Med. 2007;36:533–7.

    Article  CAS  Google Scholar 

  103. Saggini A, Chimenti S, Chiricozzi A. IL-6 as a Druggable target in psoriasis: focus on pustular variants. J Immunol Res. 2014;2014:964069.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Cho JW, Lee KS, Kim CW. Curcumin attenuates the expression of IL-1 beta, IL-6, and TNF-alpha as well as cyclin E in TNF-alpha-treated HaCaT cells; NF-kappa B and MAPKs as potential upstream targets. Int J Mol Med. 2007;19:469–74.

    CAS  PubMed  Google Scholar 

  105. Klisic A, Kavaric N, Bjelakovic B, Soldatovic I, Martinovic M, Kotur-Stevuljevic J. The association between retinol-binding protein 4 and cardiovascular risk score is mediated by waist circumference in overweight/obese adolescent girls. Acta Clin Croat. 2017;56:92–8.

    Article  PubMed  Google Scholar 

  106. Majerczyk M, Choreza P, Mizia-Stec K, Bozentowicz-Wikarek M, Brzozowska A, Arabzada H, Owczarek AJ, Szybalska A, Grodzicki T, Wiecek A, et al. Plasma level of retinol-binding protein 4, N-terminal proBNP and renal function in older patients hospitalized for heart failure. Cardiorenal Med. 2018;8:237–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kwanbunjan K, Panprathip P, Phosat C, Chumpathat N, Wechjakwen N, Puduang S, Auyyuenyong R, Henkel I, Schweigert FJ. Association of retinol binding protein 4 and transthyretin with triglyceride levels and insulin resistance in rural thais with high type 2 diabetes risk. BMC Endocr Disord. 2018;18:26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Vink RG, Roumans NJ, Mariman EC, van Baak MA. Dietary weight loss-induced changes in RBP4, FFA, and ACE predict weight regain in people with overweight and obesity. Phys Rep. 2017;5:e13450.

    Article  CAS  Google Scholar 

  109. Zhou Z, Chen H, Ju H, Sun M. Circulating retinol binding protein 4 levels in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Lipids Health Dis. 2017;16:180.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Baran A, Swiderska M, Mysliwiec H, Flisiak I. Effect of psoriasis activity and topical treatment on serum lipocalin-2 levels. J Dermatolog Treat. 2017;28:136–40.

    Article  CAS  PubMed  Google Scholar 

  111. Gul FC, Cicek D, Kaman D, Demir B, Nazik H. Changes of serum lipocalin-2 and retinol binding protein-4 levels in patients with psoriasis and Behcet's disease. Eur J Dermatol. 2015;25:195–7.

    PubMed  Google Scholar 

  112. Romani J, Caixas A, Ceperuelo-Mallafre V, Carrascosa JM, Ribera M, Rigla M, Vendrell J, Luelmo J. Circulating levels of lipocalin-2 and retinol-binding protein-4 are increased in psoriatic patients and correlated with baseline PASI. Arch Dermatol Res. 2013;305:105–12.

    Article  CAS  PubMed  Google Scholar 

  113. Karadag AS, Ertugrul DT, Kalkan G, Bilgili SG, Celik HT, Takci Z, Balahoroglu R, Calka O. The effect of acitretin treatment on insulin resistance, retinol-binding protein-4, leptin, and adiponectin in psoriasis vulgaris: a noncontrolled study. Dermatology. 2013;227:103–8.

    Article  CAS  PubMed  Google Scholar 

  114. Andersen G, Burgdorf KS, Sparso T, Borch-Johnsen K, Jorgensen T, Hansen T, Pedersen O. AHSG tag single nucleotide polymorphisms associate with type 2 diabetes and dyslipidemia: studies of metabolic traits in 7,683 white Danish subjects. Diabetes. 2008;57:1427–32.

    Article  CAS  PubMed  Google Scholar 

  115. Dahlman I, Eriksson P, Kaaman M, Jiao H, Lindgren CM, Kere J, Arner P. alpha2-Heremans-Schmid glycoprotein gene polymorphisms are associated with adipocyte insulin action. Diabetologia. 2004;47:1974–9.

    Article  CAS  PubMed  Google Scholar 

  116. Ix JH, Sharma K. Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-a, adiponectin, and AMPK. J Am Soc Nephrol. 2010;21:406–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Chattopadhyay M, Mukherjee S, Chatterjee SK, Chattopadhyay D, Das S, Majumdar SS, Mukhopadhyay S, Mukherjee S, Bhattarcharya S. Impairment of energy sensors, SIRT1 and AMPK, in lipid induced inflamed adipocyte is regulated by Fetuin a. Cell Signal. 2018;42:67–76.

    Article  CAS  PubMed  Google Scholar 

  118. Karampela I, Kandri E, Antonakos G, Vogiatzakis E, Christodoulatos GS, Nikolaidou A, Dimopoulos G, Armaganidis A, Dalamaga M. Kinetics of circulating fetuin-a may predict mortality independently from adiponectin, high molecular weight adiponectin and prognostic factors in critically ill patients with sepsis: a prospective study. J Crit Care. 2017;41:78–85.

    Article  CAS  PubMed  Google Scholar 

  119. Genc M, Can M, Guven B, Cinar S, Buyukuysal C, Acikgoz B, Mungan AG, Acikgoz S. Evaluation of serum Fetuin-a and Osteoprotegerin levels in patients with psoriasis. Indian J Clin Biochem. 2017;32:90–4.

    Article  CAS  PubMed  Google Scholar 

  120. Abella V, Scotece M, Conde J, Gomez R, Lois A, Pino J, Gomez-Reino JJ, Lago F, Mobasheri A, Gualillo O. The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases. Biomarkers. 2015;20:565–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Pietrzak A, Chabros P, Grywalska E, Kicinski P, Pietrzak-Franciszkiewicz K, Krasowska D, Kandzierski G. Serum lipid metabolism in psoriasis and psoriatic arthritis - an update. Arch Med Sci. 2019;15:369–75.

    Article  PubMed  Google Scholar 

  122. El-Hadidi H, Samir N, Shaker OG, Otb S. Estimation of tissue and serum lipocalin-2 in psoriasis vulgaris and its relation to metabolic syndrome. Arch Dermatol Res. 2014;306:239–45.

    Article  CAS  PubMed  Google Scholar 

  123. Gisondi P, Targher G, Zoppini G, Girolomoni G. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009;51:758–64.

    Article  CAS  PubMed  Google Scholar 

  124. Campanati A, Molinelli E, Ganzetti G, Giuliodori K, Minetti I, Taus M, Catani M, Martina E, Conocchiari L, Offidani A. The effect of low-carbohydrates calorie-restricted diet on visceral adipose tissue and metabolic status in psoriasis patients receiving TNF-alpha inhibitors: results of an open label controlled, prospective, clinical study. J Dermatolog Treat. 2017;28:206–12.

    Article  CAS  PubMed  Google Scholar 

  125. Boehncke WH. Systemic inflammation and cardiovascular comorbidity in psoriasis patients: causes and consequences. Front Immunol. 2018;9:579.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Boehncke S, Boehncke WH. ‘Upgrading’ psoriasis responsibly. Exp Dermatol. 2014;23:710–1.

    Article  PubMed  Google Scholar 

  127. Rajappa M, Rathika S, Munisamy M, Chandrashekar L, Thappa DM. Effect of treatment with methotrexate and coal tar on adipokine levels and indices of insulin resistance and sensitivity in patients with psoriasis vulgaris. J Eur Acad Dermatol Venereol. 2015;29:69–76.

    Article  CAS  PubMed  Google Scholar 

  128. Voloshyna I, Mounessa J, Carsons SE, Reiss AB. Effect of inhibition of interleukin-12/23 by ustekinumab on the expression of leptin and leptin receptor in human THP-1 macrophages. Clin Exp Dermatol. 2016;41:308–11.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

No

Funding

This project was supported by grants from the National Natural Science Foundation of China (No. 81872534 to Y.W. Su and No. 81874243 to M. Zhao) and the Graduate Self-Exploration and Innovation Project of Central South University of China (No. 2018zzts923 to Y. Kong).

Author information

Authors and Affiliations

  1. Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China

    Yi Kong, Suhan Zhang, Ruifang Wu, Ming Zhao & Yuwen Su

  2. Department of Cardiovascular Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China

    Xin Su & Daoquan Peng

Authors
  1. Yi Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suhan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruifang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daoquan Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ming Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuwen Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M. Zhao and Y.W. Su conceived of the scope of the review. Y. Kong was involved in the accumulation of the relevant references and drafted the manuscript. X. Su, R.F. Wu and S.H. Zhang helped draft the figure. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Ming Zhao or Yuwen Su.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kong, Y., Zhang, S., Wu, R. et al. New insights into different adipokines in linking the pathophysiology of obesity and psoriasis. Lipids Health Dis 18, 171 (2019). https://doi.org/10.1186/s12944-019-1115-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12944-019-1115-3

Keywords

  • Adipokine
  • Psoriasis
  • Obesity
  • Pathophysiology
  • Treatment

Lipids in Health and Disease

ISSN: 1476-511X