Effect of Mukitake mushroom (Panellus serotinus) on the pathogenesis of lipid abnormalities in obese, diabetic ob/ob mice
© Inoue et al.; licensee BioMed Central Ltd. 2013
Received: 30 December 2012
Accepted: 3 February 2013
Published: 14 February 2013
Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries, and several compounds that modulate the immune system, lower blood lipid levels, and inhibit tumor and viral action have been isolated. The fruiting body of Panellus serotinus (Mukitake) is recognized in Japan as one of the most delicious edible mushrooms, and previous studies have demonstrated that the dietary intake of powdered whole Mukitake or Mukitake extracts prevents the development of non-alcoholic fatty liver disease (NAFLD) in leptin-resistant db/db mice. In the present study, we evaluated the effect of the Mukitake diet on the pathogenesis of metabolic disorders in leptin-deficient ob/ob mice.
After 4 weeks of feeding, hepatomegaly, hepatic lipid accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in Mukitake-fed ob/ob mice compared with control mice. Moreover, the mild hyperlipidemia in control ob/ob mice was attenuated and the elevated atherogenic index was reduced in Mukitake-fed ob/ob mice. These effects were partly attributable to the suppression of hepatic lipogenic enzyme activity due to the Mukitake diet.
The current results showed that Mukitake supplementation is beneficial for the alleviation of NAFLD and dyslipidemia in obese, diabetic ob/ob mice.
KeywordsPanellus serotinus Atherogenic index Nonalcoholic fatty acid disease ob/ob mice
Diet contributes to the development and prevention of lifestyle-related diseases, and various mushrooms have been used in folk medicine for the treatment of lifestyle-related diseases in eastern countries[1–3]. Several lines of evidence support the nutraceutical effect of edible mushrooms, and many compounds that modulate the immune system, lower blood lipid levels, and inhibit tumors and viral action have been isolated from various mushrooms, such as Shiitake and Hatakeshimeji[1–6]. Panellus serotinus belongs to the same family of mycelia as Lentinus edodes (Shiitake) and Lyophyllum decastes (Hatakeshimeji), and its fruiting body (Mukitake) is recognized in Japan as one of the most delicious edible mushrooms. The technology for the artificial cultivation of Mukitake in plastic greenhouses has recently been developed and has enabled the constant provision of Mukitake mushrooms in the market.
Metabolic syndrome, which comprises a cluster of metabolic abnormalities, such as hyperlipidemia, diabetes mellitus, and hypertension, is a widespread and increasingly prevalent disease in industrialized countries and contributes to the increase in cardiovascular morbidity and mortality[8, 9]. Nonalcoholic fatty liver disease (NAFLD) is often associated with features of metabolic syndrome and is emerging as the most common liver disease worldwide[10–13]. Dyslipidemia is a lipid abnormality in the blood, and hyperlipidemia is prevalent due to westernized diets and the disadvantages of modern lifestyles. Insulin resistance can also lead to dyslipidemia. Many studies evaluating the effects of functional food components on the pathogenesis of obesity-related metabolic disorders have been carried out in genetic leptin-resistant db/db mice and leptin-deficient ob/ob mice[14, 15]. db/db mice have a missense mutation in the leptin receptor gene, and ob/ob mice have an inherited deficiency of the leptin gene, and they suffer from hyperphagia and develop a syndrome with multiple metabolic and hormonal disorders, including NAFLD and dyslipidemia, which shares many features with human metabolic syndrome. A recent study suggested that pathological features of liver lesions and the response to diets are slightly different between db/db and ob/ob mice.
In previous studies, we demonstrated that the dietary intake of powdered whole Mukitake or Mukitake extracts prevented the development of NAFLD, partly through the suppression of hepatic lipogenesis and normalized adipocytokine profiles, in leptin-resistant db/db mice[17, 18]. In the present study, we evaluated the effect of the Mukitake diet on the pathogenesis of metabolic disorders in leptin-deficient ob/ob mice.
Materials and methods
Animals and diets
Composition of experimental diets
Mineral mixture (AIN 76)
Vitamin mixture (AIN 76)
Mukitake powder *
Measurement of serum parameters
Serum lipoproteins were analyzed using an on-line dual enzymatic method for the simultaneous quantification of triglyceride and cholesterol using high-performance liquid chromatography at Skylight Biotech Inc. (Akita Japan), as described elsewhere. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum were measured using commercial enzyme assay kits (Wako Pure Chemicals, Tokyo, Japan). Serum adiponectin and insulin levels were measured using commercial mouse ELISA kits (Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan; Shibayagi Co. Ltd., Gunma, Japan, respectively).
Measurement of triglyceride and cholesterol levels in the liver
Assays of hepatic enzyme activity
The preparation of hepatic subcellular fractions was described previously. The enzyme activities of fatty acid synthase (FAS), glucose 6-phosphate dehydrogenase (G6PDH), and malic enzyme in the cytosomal fraction, carnitine palmitoyltransferase (CPT) in the mitochondrial fraction, and phosphatidate phosphohydrolase (PAP) in the microsomal fraction were determined as described elsewhere.
All values are expressed as the means ± standard error. The data were analyzed using a one-way ANOVA, and all differences were analyzed using the Tukey-Kramer post-hoc test (KaleidaGraph; Synergy Software, Reading, PA, USA). Differences were considered to be significant at p < 0.05.
Results and discussion
Effect of dietary Mukitake on the pathogenesis of NAFLD in ob/ob mice
Effect of dietary Mukitake on the pathogenesis of dyslipidemia in ob/ob mice
Effect of Mukitake diet on growth parameters in C57BL/6J and ob/ob mice
23.7 ± 2.5 a
54.4 ± 6.2 b
33.2 ± 1.6 a
0.432 ± 0.227
0.205 ± 0.067
13.2 ± 2.1
16.8 ± 3.7
11.3 ± 1.4
8.53 ± 0.45 a
27.0 ± 1.7 b
14.9 ± 0.7 c
1.89 ± 0.06 a
10.2 ± 1.3 b
6.73 ± 0.46 c
100 ± 5 a
273 ± 6 b
206 ± 7 c
0.0283 ± 0.0048 a
0.252 ± 0.028 b
0.157 ± 0.008 c
2.69 ± 0.34 a
12.1 ± 1.5 b
5.74 ± 0.35 c
10.0 ± 1.0 a
71.1 ± 2.7 b
36.8 ± 1.9 c
87.2 ± 4.2 a
190 ± 4 b
164 ± 5 c
(VLDL + LDL)/HDL
0.145 ± 0.010 a
0.438 ±0.015 b
0.259 ± 0.005 c
0.886 ± 0.248 a
52.1 ± 13.1 b
56.3 ± 9.8 b
29.6 ± 0.6 a
11.6 ± 0.5 b
12.3 ± 0.3 b
Effect of dietary Mukitake on hyperinsulinemia and serum adiponectin levels in ob/ob mice
Insulin resistance, as well as compensatory hyperinsulinemia, are the essential first pathologic step in the development of NAFLD and dyslipidemia[25–27]. In fact, hepatic steatosis and hyperlipidemia have been proposed to be a feature of insulin resistance syndrome along with type 2 diabetes and visceral obesity[25–27]. Adiponectin is one of the most abundant secretory proteins produced by adipose tissue in rodents and humans and is suggested to play a protective role in insulin resistance. In obese, diabetic ob/ob mice (Control group), serum insulin levels were markedly increased and serum adiponectin levels were significantly decreased compared with the C57BL/6J mice (Normal group) (Table 2). Our previous study indicated that powdered whole Mukitake and Mukitake extracts tended to alleviate hyperinsulinemia through increasing serum adiponectin levels in db/db mice[17, 18]. In the present study, however, the Mukitake diet did not affect serum adiponectin levels or improve hyperinsulinemia in ob/ob mice. The results suggest that the alleviating effect of the Mukitake diet on the pathogenesis of NAFLD and dyslipidemia appears to be independent of the adiponectin level and hyperinsulinemia in ob/ob mice.
Effect of dietary Mukitake on hepatic lipid metabolism in ob/ob mice
In conclusion, our present study showed that Mukitake supplementaion is beneficial for the inhibition of NAFLD development in leptin-deficient ob/ob mice besides in leptin-resistant db/db mice. Moreover, this is the first study showing that Mukitake has beneficial effects in attenuating possible atherosclerotic processes by reducing the atherogenic index in the serum.
Fatty acid synthase
Glucose 6-phosphate dehydrogenase
Non-alcoholic fatty liver disease
We thank Takanori Morooka and Saori Nomura for their technical assistance and Naoki Nagamori for providing Mukitake samples. This work was supported by a research grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
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