Agaricus bisporus supplementation reduces high-fat diet-induced body weight gain and fatty liver development
Obesity is a global epidemic characterized not only by excessive fat deposition but also by important complications such as nonalcoholic liver steatosis. Beneficial antiobesogenic effects have been described for some mushrooms. The current study aimed to demonstrate the protective effect of Agaricus bisporus (AB) supplementation against the metabolic alterations induced by high-fat-diet (HFD) feeding. Eight-week-old C57BL/6J mice were fed for 10 weeks with one of the following diets: (1) control diet (n = 7), (2) HFD (n = 7), (3) HFD supplemented with 5% AB (n = 9), and (4) HFD supplemented with 10% AB (n = 9). A pair-fed group was also included for the 10% AB group (n = 6). The impact of AB supplementation on food intake, body weight gain, and liver and fat pad weights was examined. Biochemical, histological, and molecular parameters were also analyzed. Dietary supplementation with 10% AB reduced the HFD-induced increase in body, epididymal, and mesenteric fat weights (p < 0.01, p < 0.05, and p < 0.05, respectively). Supplementation with AB also reduced liver damage in a dose-dependent manner (p < 0.01 and p < 0.001). This effect was confirmed by histological analysis that showed that liver steatosis was markedly reduced in mice fed with AB. The beneficial properties of 10% AB supplementation appear to be mediated through a decrease in food intake and via stimulation of mesenteric and hepatic free-fatty acid beta-oxidation, along with a decrease in epidydimal and hepatic expression of CD36. In conclusion, supplementation with AB prevents excessive body weight gain and liver steatosis induced by HFD consumption.
KeywordsAgricus bisporus Liver steatosis High-fat diet-induced obesity
We appreciate the excellent technical assistance of Judith Narro and the helpful advice from Dr. Alfredo Martinez in the histology analysis.
This work was supported by a grant from the Agencia de Desarrollo Económico de La Rioja (ADER) (project number 2014-I-IDD-00091). ADER played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Compliance with ethical standards
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures involving animals were in accordance with the ethical standards of the ethics committee on animal welfare of our institution (Comité Ético de Experimentación Animal del Centro de Investigación Biomédica de La Rioja, CEEA-CIBIR).
- 2.Anandhi R, Annadurai T, Anitha TS, Muralidharan AR, Najmunnisha K, Nachiappan V, Thomas PA, Geraldine P (2013) Antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom, Pleurotus ostreatus, and its major constituent, chrysin, in triton WR-1339-induced hypercholesterolemic rats. J Physiol Biochem 69(2):313–323. https://doi.org/10.1007/s13105-012-0215-6 CrossRefPubMedGoogle Scholar
- 3.Andersson T, Simonyte K, Andrew R, Strand M, Burén J, Walker BR, Mattsson C, Olsson T (2009) Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women. PLoS One 4(12):e8475. https://doi.org/10.1371/journal.pone.0008475 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Beck EJ, Tosh SM, Batterham MJ, Tapsell LC, Huang XF (2009) Oat beta-glucan increases postprandial cholecystokinin levels, decreases insulin response and extends subjective satiety in overweight subjects. Mol Nutr Food Res 53(10):1343–1351. https://doi.org/10.1002/mnfr.200800343 CrossRefPubMedGoogle Scholar
- 10.Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, Rizzetto M (2002) Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123(1):134–140CrossRefGoogle Scholar
- 11.Caesar R, Manieri M, Kelder T, Boekschoten M, Evelo C, Muller M, Kooistra T, Cinti S, Kleemann R, Drevon CA (2010) A combined transcriptomics and lipidomics analysis of subcutaneous, epididymal and mesenteric adipose tissue reveals marked functional differences. PLoS One 5(7):e11525. https://doi.org/10.1371/journal.pone.0011525 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.de Miranda AM, Ribeiro GM, Cunha AC, Silva LS, dos Santos RC, Pedrosa ML, Silva ME (2014) Hypolipidemic effect of the edible mushroom Agaricus blazei in rats subjected to a hypercholesterolemic diet. J Physiol Biochem 70(1):215–224. https://doi.org/10.1007/s13105-013-0295-y CrossRefPubMedGoogle Scholar
- 17.Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ (2005) Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115(5):1343–1351. https://doi.org/10.1172/JCI23621 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA, D’Agostino RB Sr, O’Donnell CJ (2007) Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham heart study. Circulation 116(1):39–48. https://doi.org/10.1161/CIRCULATIONAHA.106.675355 CrossRefPubMedGoogle Scholar
- 22.Granneman JG, Moore HP, Krishnamoorthy R, Rathod M (2009) Perilipin controls lipolysis by regulating the interactions of AB-hydrolase containing 5 (Abhd5) and adipose triglyceride lipase (Atgl). J Biol Chem 284(50):34538–34544. https://doi.org/10.1074/jbc.M109.068478M109.068478 CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Hashimoto T, Cook WS, Qi C, Yeldandi AV, Reddy JK, Rao MS (2000) Defect in peroxisome proliferator-activated receptor alpha-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. J Biol Chem 275(37):28918–28928. https://doi.org/10.1074/jbc.M910350199M910350199 CrossRefPubMedGoogle Scholar
- 28.Huang J, Ou Y, Yew TWD, Liu J, Leng B, Lin Z, Su Y, Zhuang Y, Lin J, Li X, Xue Y, Pan Y (2016) Hepatoprotective effects of polysaccharide isolated from Agaricus bisporus industrial wastewater against CCl4-induced hepatic injury in mice. Int J Biol Macromol 82:678–686. https://doi.org/10.1016/j.ijbiomac.2015.10.014 CrossRefPubMedGoogle Scholar
- 29.Hughes K (2002) Chitosan and dietary fibers. Prepared Foods. NS11-NS14Google Scholar
- 31.Jeong SC, Jeong YT, Yang BK, Islam R, Koyyalamudi SR, Pang G, Cho KY, Song CH (2010) White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats. Nutr Res 30(1):49–56. https://doi.org/10.1016/j.nutres.2009.12.003 CrossRefPubMedGoogle Scholar
- 34.Kanaya N, Kubo M, Liu Z, Chu P, Wang C, Yuan YC, Chen S (2011) Protective effects of white button mushroom (Agaricus bisporus) against hepatic steatosis in ovariectomized mice as a model of postmenopausal women. PLoS One 6(10):e26654. https://doi.org/10.1371/journal.pone.0026654 CrossRefPubMedPubMedCentralGoogle Scholar
- 38.Kozarski M, Klaus A, Niksic M, Jakovljevic D, Helsper J, VG L (2011) Antioxidative and immunomodulating activities of polysaccharide extracts of the medicinal mushrooms Agaricus bisporus, Agaricus brasiliensis, Ganoderma lucidum and Phellinus linteus. Food Chem 129(4):1667–1675. https://doi.org/10.1016/j.foodchem.2011.06.029 CrossRefGoogle Scholar
- 42.Lodhi IJ, Yin L, Jensen-Urstad AP, Funai K, Coleman T, Baird JH, El Ramahi MK, Razani B, Song H, Fu-Hsu F, Turk J, Semenkovich CF (2012) Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARgamma activation to decrease diet-induced obesity. Cell Metab 16(2):189–201. https://doi.org/10.1016/j.cmet.2012.06.013 CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Lomba A, Martinez JA, Garcia-Diaz DF, Paternain L, Marti A, Campion J, Milagro FI (2010) Weight gain induced by an isocaloric pair-fed high fat diet: a nutriepigenetic study on FASN and NDUFB6 gene promoters. Mol Genet Metab 101(2–3):273–278. https://doi.org/10.1016/j.ymgme.2010.07.017S1096-7192(10)00294-5 CrossRefPubMedGoogle Scholar
- 47.Miyoshi H, Souza SC, Zhang HH, Strissel KJ, Christoffolete MA, Kovsan J, Rudich A, Kraemer FB, Bianco AC, Obin MS, Greenberg AS (2006) Perilipin promotes hormone-sensitive lipase-mediated adipocyte lipolysis via phosphorylation-dependent and -independent mechanisms. J Biol Chem 281(23):15837–15844. https://doi.org/10.1074/jbc.M601097200 CrossRefPubMedGoogle Scholar
- 49.Moro C, Palacios I, Lozano M, D’Arrigo M, Guillamón E, Villares A, Martinez A, García-Lafuente A (2012) Anti-inflammatory activity of methanolic extracts from edible mushrooms in LPS activated RAW 264.7 macrophages. Food Chem 130:350–355. https://doi.org/10.1016/j.foodchem.2011.07.049 CrossRefGoogle Scholar
- 50.Palou M, Sanchez J, Priego T, Rodriguez AM, Pico C, Palou A (2010) Regional differences in the expression of genes involved in lipid metabolism in adipose tissue in response to short- and medium-term fasting and refeeding. J Nutr Biochem 21(1):23–33. https://doi.org/10.1016/j.jnutbio.2008.10.001S0955-2863(08)00220-9 CrossRefGoogle Scholar
- 52.Park MK, Han Y, Kim MS, Seo E, Kang S, Park SY, Koh H, Kim DK, Lee HJ (2012) Reduction of food intake by Fenofibrate is associated with cholecystokinin release in long-Evans Tokushima rats. Korean J Physiol Pharmacol 16(3):181–186. https://doi.org/10.4196/kjpp.2012.16.3.181 CrossRefPubMedPubMedCentralGoogle Scholar
- 55.Saggerson D (2008) Malonyl-CoA, a key signaling molecule in mammalian cells. Annu Rev Nutr 28:253–272. https://doi.org/10.1146/annurev.nutr.28.061807.155434 CrossRefPubMedGoogle Scholar
- 56.Saito N, Kimura S, Miyamoto T, Fukushima S, Amagasa M, Shimamoto Y, Nishioka C, Okamoto S, Toda C, Washio K, Asano A, Miyoshi I, Takahashi E, Kitamura H (2017) Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice. Biochem Biophys Rep 9:322–329. https://doi.org/10.1016/j.bbrep.2017.01.009 CrossRefPubMedPubMedCentralGoogle Scholar
- 60.Valdecantos MP, Perez-Matute P, Gonzalez-Muniesa P, Prieto-Hontoria PL, Moreno-Aliaga MJ, Martinez JA (2012) Lipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial function. J Nutr Biochem 23(12):1676–1684. https://doi.org/10.1016/j.jnutbio.2011.11.011 CrossRefPubMedGoogle Scholar