A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation
© Bjørndal et al.; licensee BioMed Central Ltd. 2013
Received: 31 July 2013
Accepted: 24 September 2013
Published: 7 October 2013
There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNFα).
hTNFα mice (C57BL/6 hTNFα) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma.
The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ∆6 and ∆9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-γ level was observed. Plasma carnitine and the carnitine precursor γ-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal β-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice.
The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.
Dietary proteins and the bioactive peptides generated from proteins, either formed naturally in the gut or delivered in the diet as hydrolyzed proteins, may have a number of important effects beyond their role as sources of amino acids and energy . Studies on fish peptides have demonstrated antihypertensive [2–5], antioxidant [6–9], and immunomodulating effects , as well as reparative properties in the intestine [11, 12]. Hydrolyzed proteins from plant and fish have been demonstrated to alter the cholesterol and lipid metabolism in rodent studies, and to reduce plasma cholesterol and triglyceride levels [1, 13–15]. In addition, we previously found a reduction in hepatic ∆5 and ∆6 desaturase mRNA expression in obese Zucker rats by a fish protein hydrolysate (FPH) diet .
There is an inter-organ transport of fatty acids, and major tissues in fatty acid metabolism from an energy point of view are the gut, white adipose tissue (WAT), liver and muscle. The liver plays a major role in the desaturation and elongation processes that determine the fatty acid composition during de novo lipogenesis. Studies have indicated that diet-induced alterations in the membrane phospholipid composition has important effects on inflammation, in particular through increased anti-inflammatory prostaglandin and resolvine production from n-3 polyunsaturated fatty acids (PUFAs) . The ∆9 desaturase steroyl-CoA desaturase 1 (SCD1) is important for the generation of monounsaturated fatty acids during lipogenesis. It plays a role in inflammatory regulation, and its upregulation is correlated to many metabolic diseases including obesity and insulin resistance [18, 19]. Previous studies indicate that dietary protein composition plays an important role in the regulation of fatty acid desaturation as well as cholesterol metabolism [14, 20, 21]. Thus, protein hydrolysate diets could potentially target lipogenesis and desaturation and thereby positively influence metabolic disturbances.
As hydrolyzed proteins have the ability to modulate both lipid metabolism, and inflammation processes, we investigated in the present study whether a 15% FPH diet high in glycine and taurine could counteract the effects of tumor necrosis factor alpha (TNFα) overexpression. Mice transgenic for human TNFα (hTNFα) have previously been shown to display dyslipidemia, altered lipid composition, and reduced activation of peroxisome proliferator-activated receptor alpha (PPARα) regulated genes . In the present study, we show that the administration of FPH to hTNFα mice fed a high-fat diet affected fatty acid composition in liver and WAT with a concurrent increase in the fatty acid anti-inflammatory index. In addition, plasma carnitine and short-chained acylcarnitine esters, and hepatic peroxisomal fatty acid oxidation were increased, while lipogenesis was reduced.
The effect of FPH on feed intake and blood lipids
Fasting lipid levels in TNFα mice given a control- or a FPH-high-fat diet for two weeks
1.74 ± 0.18
1.71 ± 0.18
8.2 ± 1.3
7.7 ± 0.8
0.50 ± 0.15
0.58 ± 0.10
25.3 ± 2.8
29.3 ± 4.6
1.67 ± 0.23
1.66 ± 0.14
18.9 ± 0.78
19.0 ± 0.52
Weight gain and feed intake in TNFα mice given control- or FPH-diets for two weeks
Feed efficiency (weight gain/feed intake)
1.40 ± 0.55
0.041 ± 0.016
2.60 ± 0.89*
0.067 ± 0.023
Fatty acid composition in liver and WAT
Fatty acid composition in liver and WAT of mice given control- or FPH-diets for 2 weeks and fasted over night
Fatty acids % (w/w)
34.57 ± 0.74
34.81 ± 0.87
32.35 ± 1.08
34.35 ± 1.15*
21.42 ± 0.35
22.19 ± 0.49*
25.26 ± 0.83
26.13 ± 1.31
12.02 ± 0.55
11.49 ± 0.57
4.61 ± 0.45
5.73 ± 0.55**
25.43 ± 0.89
24.25 ± 1.31
48.62 ± 1.17
47.83 ± 2.35
1.03 ± 0.13
1.03 ± 0.12
4.74 ± 0.34
4.51 ± 0.46
1.60 ± 0.08
1.32 ± 0.09***
2.22 ± 0.08
2.04 ± 0.04**
21.77 ± 0.75
21.01 ± 1.15
40.35 ± 1.40
40.08 ± 5.53
∑ n- 6 PUFAs
31.05 ± 0.59
30.52 ± 0.07
17.61 ± 1.38
16.21 ± 1.35
16.00 ± 0.54
17.03 ± 0.75*
16.70 ± 1.41
15.38 ± 1.30
0.90 ± 0.06
0.76 ± 0.05**
0.15 ± 0.01
0.12 ± 0.01*
12.96 ± 0.79
11.79 ± 0.57*
0.34 ± 0.04
0.30 ± 0.04
0.34 ± 0.01
0.25 ± 0.01***
0.07 ± 0.01
0.06 ± 0.01*
∑ n- 3 PUFAs
8.73 ± 0.65
10.24 ± 0.68**
1.28 ± 0.10
1.49 ± 0.25
0.42 ± 0.03
0.50 ± 0.05*
0.89 ± 0.06
0.98 ± 0.14
C20:5n- 3 (EPA)
0.29 ± 0.03
0.57 ± 0.10***
0.03 ± 0.01
0.06 ± 0.02**
0.29 ± 0.02
0.42 ± 0.02***
0.07 ± 0.01
0.09 ± 0.02*
C22:6n- 3 (DHA)
7.60 ± 0.65
8.60 ± 0.60*
0.24 ± 0.03
0.32 ± 0.07
∑ n- 3:∑ n- 6 ratio
0.28 ± 0.35
0.34 ± 0.02**
0.07 ± 0.01
0.09 ± 0.01**
Anti-inflammatory index and plasma cytokines
Hepatic fatty acid oxidation and synthesis
Precursor of carnitine and carnitine esters in plasma
Several investigations have reported an effect of inflammatory cytokines on lipid metabolism [23–26]. The target genes of PPARα, an important transcription factor regulating the fasting response, were downregulated in the liver of TNFα overexpressing mice . As PPARα regulates both the lipid- and amino acid metabolism, we have in the present study investigated whether an FPH-diet can counteract TNFα-induced metabolic aberrations. We observed a significant effect on the hepatic and WAT fatty acid composition of FPH-fed mice, linked to effects on the gene expression or activity of genes involved in desaturation and lipogenesis. This demonstrates that casein- and salmon derived sources of protein differentially influence lipid metabolism in hTNFα mice.
The higher activity of CPT-II and ACOX1 accompanied with higher plasma levels of short-and medium carnitine esters in mice fed FPH suggest that this diet was able to improve the hepatic fatty acid oxidation capacities compared to a casein diet. Acetyl-CoA could potentially be used for keton body production, as the gene expression of the mitochondrial HMG-CoA synthase was upregulated. Alternatively, the observed higher level of plasma L-carnitine in FPH-fed mice could facilitate mitochondrial efflux of β-oxidation products. L-carnitine supplementation has previously been shown to relieve lipid overload and increase glucose sensitivity in obese mice .
A cholesterol lowering effect of FPH diets compared to casein diets have previously been observed in rodents, and may be due to decreased intestinal absorption concomitant with increased hepatic excretion of cholesterol and bile [28, 29]. FPH has in some rodent studies also resulted in lower plasma triacylglycerol (TAG) levels [15, 30]. It was therefore of importance to note that in this study FPH did not reduce plasma cholesterol or TAG levels. The reason for this is not clear, but one possibility is that the mitochondrial CPT-II activity was marginally higher with FPH mice than in control mice (20%) and that no significantly elevated gene expression of the PPARα activated genes Cpt1a, Cpt2, nor Hadha were observed. The observed lower lipogenesis with FPH vs. casein, similar to observations with vegetable protein diets in rats , was not sufficient to lower plasma TAG levels (Figure 3c). Also, no effect was seen on genes involved in cholesterol and bile production. It might be that a longer feeding period than two weeks is required to get a more pronounced effect on mitochondrial fatty acid oxidation and thereby overcome the hypertriglyceridemia in the TNFα mice. Indeed, in another experiment with male C57BL/6 normolipidemic mice treated for 6 weeks, the plasma TAG concentration was 28% lower in 15% FPH fed mice than in casein fed mice, while cholesterol was unchanged (RK Berge, data to be published). Interestingly, the male mice gained less weight with a higher feed intake than the control group, while in the current study the female FPH mice gained more weight than control mice. This might indicate sex-specific effects of FPH.
In the present study we show that the fatty acid composition was different in the liver and WAT of mice fed the FPH diet compared to the control diet, although the diets did not differ substantially in fatty acid composition. In the liver this can at least partly be due to higher mitochondrial and peroxisomal fatty acid oxidation. The ∆5 and ∆6 fatty acid indices were higher in mice fed FPH than casein, thus the changes in the fatty acid composition could also be due to differences in the activities of ∆5 and ∆6 desaturases. The hepatic gene expression of ∆6 desaturase was, however, lower than control whereas the mRNA level of ∆5 desaturase was identical after FPH administration. The lower gene expression levels could be a negative regulatory response to a higher level of unsaturated fatty acids. This is in agreement with a previous study demonstrating that in human WAT the gene expression of ∆5 and ∆6 desaturase was poorly reflected in the corresponding indices . In contrast, the different SCD1 indices was linked to the gene expression level of Scd1. Thus, the lower hepatic gene expression of Scd1 in FPH-fed compared to casein-fed mice might explain the corresponding low SCD1-index in WAT from FPH-mice. Interestingly, SCD1 has been shown to regulate inflammation and stress in several cell types . Also, a low SCD1 expression level has been indicated to protect against obesity and insulin resistance, while the opposite is true for high SCD1 levels [18, 19]. Particularly, a high WAT 18:1/18:0 ratio has been linked to increased probability of insulin resistance in older men . Thus, the observed reduction in the 18:1/18:0 ratio in WAT of FPH-fed mice could indicate effects on fatty acid denaturation beneficial to health.
Amino acid composition, fatty acid composition, and vitamin D content of the experimental diets
n-3 PUFA/ n-6 PUFA
Treatment with FPH resulted in lower hepatic and WAT levels of long-chain n-6 fatty acids compared to a casein control. The anti-inflammatory fatty acid index was thereby increased both in liver and WAT. As the plasma level of INF-γ was reduced in the FPH-treated mice while other cytokines measured were unchanged, FPH may have an anti-inflammatory potential perhaps linked to its effect on fatty acid metabolism. The main effect of feeding TNFα mice a FPH diet was on fatty acid composition, lipogenesis, β-oxidation and acylcarnitines. This indicates that regulation of lipid metabolism is important for the bioactivity of protein hydrolysates of marine origin.
Female transgenic mice expressing human TNFα (hTNFα) were used (Taconic, Germantown, USA). This mouse line is generated in the strain C57BL/6, and express low levels of hTNFα . The experiments were performed in accordance with, and under the approval of, the Norwegian State Board for Biological Experiments, the Guide for the Care and Use of Laboratory Animals, and the Guidelines of the Animal Welfare Act. The mice were divided into two experimental groups of five animals each with comparable mean body weight and were housed five animals per cage under constant temperature (22 ± 2°C) and humidity (55 ± 5%). They were exposed to a 12 h light–dark cycle (light from 07.00 to 19.00) and had unrestricted access to tap water and food. The mice were acclimatized to these conditions for one week before the start of the experiment.
Composition of the experimental diets
Control (g/kg of diet)
FPH (g/kg of diet)
AIN-93G mineral mix
AIN-93 vitamin mix
Plasma and hepatic lipids
Liver lipids were extracted according to Blight and Dyer , evaporated under nitrogen and redissolved in isopropanol before analysis. Lipids were measured enzymatically in plasma samples and hepatic extracts on a Hitachi 917 system (Roche Diagnostics GmbH, Mannheim, Germany) using the triacylglycerol (GPO-PAP) and cholesterol kit (CHOD-PAP) from Roche Diagnostics, the free fatty acid (FFA) kit from DiaSys Diagnostic Systems GmbH (Holzheim, Germany), and the phospholipid kit from bioMerieux SA (Marcy l’Etoile, France).
Hepatic and WAT fatty acid composition
Total hepatic and WAT fatty acid composition was analyzed as described previously . The anti-inflammatory fatty acid index was calculated as ((C22:5n-3 + C22:6n-3 + C20:3n-6 + C20:5n-3)/C20:4n-6)*100 .
Amino acid composition in the diet
The amino acids in the diets were determined after hydrolysis in 6 m-HCl at 110°C for 22 h and pre-derivatisation with phenylisothiocyanate according to the method of Cohen & Strydom . The supernatant was filtered and amino acids were characterised by a Biochrom 20 plus amino acid analyser as previously described .
Hepatic enzyme activities
The livers were homogenized and fractionated as described earlier . The activities of carnitine palmitoyltransferase–II (CPT-II) , acyl-CoA oxidase 1 (ACOX1) and fatty acid synthase (FASN) were measured in the post-nuclear fraction as described by Skorve et al..
Plasma carnitine composition and cytokines
Free carnitine, short-, medium-, and long-chain acylcarnitines, and the precursors for carnitine, trimethyllysine and γ-butyrobetaine, were analysed in plasma using LC/MS/MS as described previously . The cytokines INF-γ, IL-1b, IL-2, IL-4, IL-5, IL-10, IL-12, and GM-CST were assessed in a 96-well plate assay using custom made eight-plex kits (Millipore Corp., St. Charles, IL, USA). Cytokines IL-4, IL-10 and IL-12 did not give a result due to more than two samples below detection limit. Plasma adiponectin was measured using a single-plex kit (Millipore). The analysis was performed on undiluted plasma samples, in an overnight protocol according to the manufacturer’s recommendations, using the Bio-Plex 200 system (BioRad, Hercules, CA, USA).
Gene expression analysis
Total cellular RNA was purified from frozen liver samples, and cDNA was produced as previously described . Real-time PCR was performed with Sarstedt 384 well multiply-PCR Plates (Sarstedt Inc., Newton, NC, USA) on the following genes, using probes and primers from Applied Biosystems (Foster City, CA, USA): acetyl-CoA carboxylase alpha (Acaca, Mm01304277_m1), Acox1 (Mm00443579), trifunctional protein, alpha subunit (Hadha, Mm00805228_m1), CD36 antigen (CD36 (Fat), Mm00432403), Cpt1a (Mm00550438), Cpt2 (Mm00487202), cytochrome P450, family 7, subfamily A, polypeptide 1 (Cyp7a1, Mm00484152), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgc1, Mm00524111), Hmgc2 (Mm00550050), low density lipoprotein receptor (Ldlr, Mm00440169), stearoyl-CoA desaturase 1 (Scd1, Mm00772290_m1), or Solaris qPCR Gene Expression Assays (Thermo Fisher Scientific Inc.,Waltham, MA, USA): fatty acid desaturase 1 (Fads1, AX-064722-00), Fads2/∆6 fatty acid desaturase (AX-049816-00), arylacetamide deacetylase (Aadac, AX-049058-00). Three different reference genes were included: 18 s (Kit-FAM-TAMRA (Reference RT-CKFT-18 s)) from Eurogentec, Belgium, glyceraldehyde-3-phosphate dehydrogenase (Gapdh, Mm99999915_g1) from Applied Biosystems, and ribosomal protein, large, P0 (Rplp0, Gene ID 11837) from Thermo Fisher Scientific. NormFinder was used to evaluate the reference genes, and data normalized to 18 s are presented.
Data sets were analyzed using Prism Software (Graph-Pad Software, San Diego, CA) to generate the figures and determine statistical significance. The results are shown as means with their standard deviations (SD). Student’s t-test and Mann–Whitney test, for parametric data and non-parametric data, respectively, were performed to evaluate statistical differences between the two groups. P-values < 0.05 were considered significant.
We thank Kari Williams, Liv Kristine Øysæd, Randi Sandvik, Svein Krüger, and Torunn Eide for excellent technical assistance. This work was supported by grants from NordForsk, grant no. 070010, MitoHealth; EEA Polish-Norwegian Research Fund, grant no. PNRF-104-Al-1/07; the Research Council of Norway, grant no. 190287/110; and the European Community’s Seventh Framework Programme (FP7/2007-2013), grant no. 201668, AtheroRemo.
- Moller NP, Scholz-Ahrens KE, Roos N, Schrezenmeir J: Bioactive peptides and proteins from foods: indication for health effects. Eur J Nutr. 2008, 47: 171-182. 10.1007/s00394-008-0710-2View ArticlePubMedGoogle Scholar
- Hatanaka A, Miyahara H, Suzuki KI, Sato S: Isolation and identification of antihypertensive peptides from antarctic krill tail meat hydrolysate. J Food Sci. 2009, 74: H116-H120. 10.1111/j.1750-3841.2009.01138.xView ArticlePubMedGoogle Scholar
- Kim SK, Ngo DH, Vo TS: Marine fish-derived bioactive peptides as potential antihypertensive agents. Adv Food Nutr Res. 2012, 65: 249-260.View ArticlePubMedGoogle Scholar
- Li Y, Zhou J, Huang K, Sun Y, Zeng X: Purification of a novel angiotensin I-converting enzyme (ACE) inhibitory peptide with an antihypertensive effect from loach (Misgurnus anguillicaudatus). J Agric Food Chem. 2012, 60: 1320-1325. 10.1021/jf204118nView ArticlePubMedGoogle Scholar
- Ngo DH, Ryu B, Vo TS, Himaya SW, Wijesekara I, Kim SK: Free radical scavenging and angiotensin-I converting enzyme inhibitory peptides from Pacific cod (Gadus macrocephalus) skin gelatin. Int J Biol Macromol. 2011, 49: 1110-1116. 10.1016/j.ijbiomac.2011.09.009View ArticlePubMedGoogle Scholar
- Nazeer RA, Sampath Kumar NS, Jai Ganesh R: In vitro and in vivo studies on the antioxidant activity of fish peptide isolated from the croaker (Otolithes ruber) muscle protein hydrolysate. Peptides. 2012, 35: 261-268. 10.1016/j.peptides.2012.03.028View ArticlePubMedGoogle Scholar
- Najafian L, Babji AS: A review of fish-derived antioxidant and antimicrobial peptides: their production, assessment, and applications. Peptides. 2012, 33: 178-185. 10.1016/j.peptides.2011.11.013View ArticlePubMedGoogle Scholar
- Sampath Kumar NS, Nazeer RA, Jaiganesh R: Purification and identification of antioxidant peptides from the skin protein hydrolysate of two marine fishes, horse mackerel (Magalaspis cordyla) and croaker (Otolithes ruber). Amino Acids. 2012, 42: 1641-1649. 10.1007/s00726-011-0858-6View ArticlePubMedGoogle Scholar
- Yang R, Wang J, Liu Z, Pei X, Han X, Li Y: Antioxidant effect of a marine oligopeptide preparation from chum salmon (Oncorhynchus keta) by enzymatic hydrolysis in radiation injured mice. Mar Drugs. 2011, 9: 2304-2315. 10.3390/md9112304PubMed CentralView ArticlePubMedGoogle Scholar
- Duarte J, Vinderola G, Ritz B, Perdigon G, Matar C: Immunomodulating capacity of commercial fish protein hydrolysate for diet supplementation. Immunobiology. 2006, 211: 341-350. 10.1016/j.imbio.2005.12.002View ArticlePubMedGoogle Scholar
- Fitzgerald AJ, Rai PS, Marchbank T, Taylor GW, Ghosh S, Ritz BW, Playford RJ: Reparative properties of a commercial fish protein hydrolysate preparation. Gut. 2005, 54: 775-781. 10.1136/gut.2004.060608PubMed CentralView ArticlePubMedGoogle Scholar
- Marchbank T, Limdi JK, Mahmood A, Elia G, Playford RJ: Clinical trial: protective effect of a commercial fish protein hydrolysate against indomethacin (NSAID)-induced small intestinal injury. Aliment Pharmacol Ther. 2008, 28: 799-804. 10.1111/j.1365-2036.2008.03783.xView ArticlePubMedGoogle Scholar
- Rigamonti E, Parolini C, Marchesi M, Diani E, Brambilla S, Sirtori CR, Chiesa G: Hypolipidemic effect of dietary pea proteins: Impact on genes regulating hepatic lipid metabolism. Mol Nutr Food Res. 2010, 54 (Suppl 1): S24-S30.View ArticlePubMedGoogle Scholar
- Sugiyama K, Ohkawa S, Muramatsu K: Relationship between amino acid composition of diet and plasma cholesterol level in growing rats fed a high cholesterol diet. J Nutr Sci Vitaminol (Tokyo). 1986, 32: 413-423. 10.3177/jnsv.32.413View ArticleGoogle Scholar
- Shukla A, Bettzieche A, Hirche F, Brandsch C, Stangl GI, Eder K: Dietary fish protein alters blood lipid concentrations and hepatic genes involved in cholesterol homeostasis in the rat model. Br J Nutr. 2006, 96: 674-682.PubMedGoogle Scholar
- Wergedahl H, Liaset B, Gudbrandsen OA, Lied E, Espe M, Muna Z, Mork S, Berge RK: Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA:cholesterol acyltransferase activity in liver of Zucker rats. J Nutr. 2004, 134: 1320-1327.PubMedGoogle Scholar
- Calder PC: n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006, 83: 1505S-1519S.PubMedGoogle Scholar
- Liu X, Strable MS, Ntambi JM: Stearoyl CoA desaturase 1: role in cellular inflammation and stress. Adv Nutr. 2011, 2: 15-22. 10.3945/an.110.000125PubMed CentralView ArticlePubMedGoogle Scholar
- Yokoyama S, Hosoi T, Ozawa K: Stearoyl-CoA Desaturase 1 (SCD1) is a key factor mediating diabetes in MyD88-deficient mice. Gene. 2012, 497: 340-343. 10.1016/j.gene.2012.01.024View ArticlePubMedGoogle Scholar
- De Gomez Dumm IN, De Alaniz MJ, Brenner RR: Effect of diet on linoleic acid desaturation and on some enzymes of carbohydrate metabolism. J Lipid Res. 1970, 11: 96-101.PubMedGoogle Scholar
- Brenner RR: Regulatory function of delta6 desaturate – key enzyme of polyunsaturated fatty acid synthesis. Adv Exp Med Biol. 1977, 83: 85-101. 10.1007/BF00802814View ArticlePubMedGoogle Scholar
- Glosli H, Gudbrandsen OA, Mullen AJ, Halvorsen B, Rost TH, Wergedahl H, Prydz H, Aukrust P, Berge RK: Down-regulated expression of PPARalpha target genes, reduced fatty acid oxidation and altered fatty acid composition in the liver of mice transgenic for hTNFalpha. Biochim Biophys Acta. 2005, 1734: 235-246. 10.1016/j.bbalip.2005.02.011View ArticlePubMedGoogle Scholar
- Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, Scott DK, O’Doherty RM: Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes. 2010, 59: 347-357. 10.2337/db09-0016PubMed CentralView ArticlePubMedGoogle Scholar
- Stienstra R, Duval C, Müller M, Kersten S: PPARs, obesity and inflammation. PPAR Res. 2007, 2007: 95974PubMed CentralView ArticlePubMedGoogle Scholar
- Stienstra R, Saudale F, Duval C, Keshtkar S, Groener JE, van Rooijen N, Staels B, Kersten S, Muller M: Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity. Hepatology. 2010, 51: 511-522. 10.1002/hep.23337View ArticlePubMedGoogle Scholar
- Kim MS, Sweeney TR, Shigenaga JK, Chui LG, Moser A, Grunfeld C, Feingold KR: Tumor necrosis factor and interleukin 1 decrease RXRalpha, PPARalpha, PPARgamma, LXRalpha, and the coactivators SRC-1, PGC-1alpha, and PGC-1beta in liver cells. Metabolism. 2007, 56: 267-279. 10.1016/j.metabol.2006.10.007View ArticlePubMedGoogle Scholar
- Power RA, Hulver MW, Zhang JY, Dubois J, Marchand RM, Ilkayeva O, Muoio DM, Mynatt RL: Carnitine revisited: potential use as adjunctive treatment in diabetes. Diabetologia. 2007, 50: 824-832. 10.1007/s00125-007-0605-4View ArticlePubMedGoogle Scholar
- Hosomi R, Fukunaga K, Arai H, Kanda S, Nishiyama T, Yoshida M: Fish protein decreases serum cholesterol in rats by inhibition of cholesterol and bile acid absorption. J Food Sci. 2011, 76: H116-H121. 10.1111/j.1750-3841.2011.02130.xView ArticlePubMedGoogle Scholar
- Liaset B, Hao Q, Jorgensen H, Hallenborg P, Du ZY, Ma T, Marschall HU, Kruhoffer M, Li R, Li Q: Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome. J Biol Chem. 2011, 286: 28382-28395. 10.1074/jbc.M111.234732PubMed CentralView ArticlePubMedGoogle Scholar
- Liaset B, Madsen L, Hao Q, Criales G, Mellgren G, Marschall HU, Hallenborg P, Espe M, Froyland L, Kristiansen K: Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats. Biochim Biophys Acta. 2009, 1791: 254-262. 10.1016/j.bbalip.2009.01.016View ArticlePubMedGoogle Scholar
- Sjogren P, Sierra-Johnson J, Gertow K, Rosell M, Vessby B, de Faire U, Hamsten A, Hellenius ML, Fisher RM: Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance. Diabetologia. 2008, 51: 328-335. 10.1007/s00125-007-0876-9View ArticlePubMedGoogle Scholar
- Hayward MD, Jones BK, Saparov A, Hain HS, Trillat AC, Bunzel MM, Corona A, Li-Wang B, Strenkowski B, Giordano C: An extensive phenotypic characterization of the hTNFalpha transgenic mice. BMC Physiol. 2007, 7: 13- 10.1186/1472-6793-7-13PubMed CentralView ArticlePubMedGoogle Scholar
- Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959, 37: 911-917. 10.1139/o59-099View ArticlePubMedGoogle Scholar
- Chavali SR, Zhong WW, Utsunomiya T, Forse RA: Decreased production of interleukin-1-beta, prostaglandin-E2 and thromboxane-B2, and elevated levels of interleukin-6 and −10 are associated with increased survival during endotoxic shock in mice consuming diets enriched with sesame seed oil supplemented with Quil-A saponin. Int Arch Allergy Immunol. 1997, 114: 153-160. 10.1159/000237661View ArticlePubMedGoogle Scholar
- Cohen SA, Strydom DJ: Amino acid analysis utilizing phenylisothiocyanate derivatives. Anal Biochem. 1988, 174: 1-16. 10.1016/0003-2697(88)90512-XView ArticlePubMedGoogle Scholar
- Berge RK, Flatmark T, Osmundsen H: Enhancement of long-chain acyl-CoA hydrolase activity in peroxisomes and mitochondria of rat liver by peroxisomal proliferators. Eur J Biochem. 1984, 141: 637-644. 10.1111/j.1432-1033.1984.tb08239.xView ArticlePubMedGoogle Scholar
- Madsen L, Froyland L, Dyroy E, Helland K, Berge RK: Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation. J Lipid Res. 1998, 39: 583-593.PubMedGoogle Scholar
- Skorve J, al-Shurbaji A, Asiedu D, Bjorkhem I, Berglund L, Berge RK: On the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats. J Lipid Res. 1993, 34: 1177-1185.PubMedGoogle Scholar
- Bjorndal B, Burri L, Wergedahl H, Svardal A, Bohov P, Berge RK: Dietary supplementation of herring roe and milt enhances hepatic fatty acid catabolism in female mice transgenic for hTNFalpha. Eur J Nutr. 2011, 51: 741-753.View ArticlePubMedGoogle Scholar
- Vigerust NF, Cacabelos D, Burri L, Berge K, Wergedahl H, Christensen B, Portero-Otin M, Viste A, Pamplona R, Berge RK, Bjørndal B: Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks. J Nutr Biochem. 2011, 23: 1384-1393.View ArticleGoogle Scholar
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