Published 12 issues per year
ISSN Print: 1521-9437
ISSN Online: 1940-4344
Indexed in
Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Polysaccharides Suppressed Adipogenesis and Stimulated Lipolysis in HPA-v and 3T3-L1 Adipocytes
ABSTRACT
Ganoderma lucidum polysaccharides (GLP) are one of the major bioactive components with many beneficial properties. In the present study we aimed to systematically evaluate the effects of GLP on lipid metabolism in human (HPA-v) and murine adipocytes (3T3-L1). Cell viability was assessed by MTT assay. Lipid accumulation in mature adipocytes were evaluated by ORO staining and quantified using the triglyceride (TG) assay. Lipolysis was investigated by measuring the free glycerol released in the cell culture medium after treatments. The mRNA and protein levels of key genes regulating lipid metabolism were determined by qRT-PCR and western blotting in HPA-v cells. ORO staining showed that GLP suppressed lipid accumulation similarly in both HPA-v and 3T3-L1 cells. TG assay confirmed that GLP significantly inhibited cell differentiation (p < 0.001). The lipolysis assay showed that GLP enhanced triglyceride hydrolysis in both adipocytes (p < 0.05). GLP stimulated AMPK phosphorylation, which promoted the phosphorylation of ACC1, its downstream target. qRT-PCR and western blotting showed that the genes encoding transcription factors for adipocyte differentiation (PPARγ, C/EBPα, and SREBPlc) and certain adipogenic genes (ACC1, PLIN1, and FASN) were downregulated (p < 0.05). The lipolytic gene HSL was upregulated and highly phosphorylated (activated) at mRNA and protein levels, respectively, upon GLP treatment. These results suggested that GLP possessed beneficial antiadipogenic effects and can potentially be developed into antiobesity products.
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Gonzalez-Muniesa P, Martinez-Gonzalez MA, Hu FB, Despres JP, Matsuzawa Y, Loos RJF, Moreno LA, Bray GA, Martinez JA. Obesity. Nat Rev Dis Primers. 2017;3:1-16.
-
Gregg EW, Shaw JE. Global health effects of overweight and obesity. N Engl J Med. 2017;377(1):80-1.
-
Garg SK, Maurer H, Reed K, Selagamsetty R. Diabetes and cancer: Two diseases with obesity as a common risk factor. Diabetes Obes Metab. 2014;16(2):97-110.
-
Smith MM, Minson CT. Obesity and adipokines: Effects on sympathetic overactivity. J Physiol. 2012;590(8):1787-801.
-
Farmer SR. Transcriptional control of adipocyte formation. Cell Metab. 2006;4(4):263-73.
-
Badeau RM, Honka MJ, Lautamaki R, Stewart M, Kangas AJ, Soininen P, Ala-Korpela M, Nuutila P. Systemic metabolic markers and myocardial glucose uptake in type 2 diabetic and coronary artery disease patients treated for 16 weeks with rosiglitazone, a PPARgamma agonist. Ann Med. 2014;46(1):18-23.
-
Zhang BB, Zhou G, Li C. AMPK: An emerging drug target for diabetes and the metabolic syndrome. Cell Metab. 2009;9(5):407-16.
-
Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48(7):e245.
-
Kim EJ, Lee DH, Kim HJ, Lee SJ, Ban JO, Cho MC, Jeong HS, Yang Y, Hong JT, Yoon DY. Thiacremonone, a sulfur compound isolated from garlic, attenuates lipid accumulation partially mediated via AMPK activation in 3T3-l1 adipocytes. J Nutr Biochem. 2012;23(12):1552-8.
-
Hong SW, Lee J, Park SE, Rhee EJ, Park CY, Oh KW, Park SW, Lee WY. Activation of ampactivated protein kinase attenuates tumor necrosis factor-alpha-induced lipolysis via protection of perilipin in 3T3-l1 adipocytes. Endocrinol Metab (Seoul). 2014;29(4):553-60.
-
Kim SO, Sakchaisri K, Asami Y, Ryoo IJ, Choo SJ, Yoo ID, Soung NK, Kim YS, Jang JH, Kim BY, Ahn JS. Illudins c2 and c3 stimulate lipolysis in 3T3-l1 adipocytes and suppress adipogenesis in 3T3-l1 preadipocytes. J Nat Prod. 2014;77(4): 744-50.
-
Kennett GA, Clifton PG. New approaches to the pharmacological treatment of obesity: Can they break through the efficacy barrier? Pharmacol Biochem Behav. 2010;97(1):63-83.
-
Chang ST, Wasser SP. Current and future research trends in agricultural and biomedical applications of medicinal mushrooms and mushroom products (review). Int J Med Mushrooms. 2018;20(12):1121-33.
-
Wasser SP. Medicinal mushrooms in human clinical studies. Part I. Anticancer, oncoimmunological, and immunomodulatory activities: A review. Int J Med Mushrooms. 2017;19(4):279-317.
-
Sanodiya BS, Thakur GS, Baghel RK, Prasad GB, Bisen PS. Ganoderma lucidum: A potent pharmacological macrofungus. Curr Pharm Biotechnol. 2009;10(8):717-42.
-
Soccol CR, Bissoqui LY, Rodrigues C, Rubel R, Sella SR, Leifa F, de Souza Vandenberghe LP, Soccol VT. Pharmacological properties of biocompounds from spores of the lingzhi or reishi medicinal mushroom Ganoderma lucidum (Agaricomycetes): A review. Int J Med Mushrooms. 2016;18(9):757-67.
-
Xu Z, Chen X, Zhong Z, Chen L, Wang Y. Ganoderma lucidum polysaccharides: Immunomodulation and potential anti-tumor activities. Am J Chin Med. 2011;39(1):15-27.
-
El-Sherif NF, Ahmed SA, Ibrahim AK, Habib ES, El-Fallal AA, El-Sayed AK, Wahba AE. Ergosterol peroxide from the Egyptian red lingzhi or reishi mushroom, Ganoderma resinaceum (Agaricomycetes), showed preferred inhibition of mcf-7 over mda-mb-231 breast cancer cell lines. Int J Med Mushrooms. 2020;22(4):389-96.
-
Zolj S, Smith MP, Goines JC, Ali TS, Huff MO, Robinson DL, Lau JM. Antiproliferative effects of a triterpene-enriched extract from lingzhi or reishi medicinal mushroom, Ganoderma lucidum (Agaricomycetes), on human lung cancer cells. Int J Med Mushrooms. 2018;20(12):1173-83.
-
Rubel R, Santa HSD, Dos Santos LF, Fernandes LC, Figueiredo BC, Soccol CR. Immunomodulatory and antitumoral properties of Ganoderma lucidum and Agaricus brasiliensis (Agaricomycetes) medicinal mushrooms. Int J Med Mushrooms. 2018;20(4):393-403.
-
Ma HT, Hsieh JF, Chen ST. Anti-diabetic effects of Ganoderma lucidum. Phytochemistry. 2015;114:109-13.
-
Zheng Y, Bai L, Zhou Y, Tong R, Zeng M, Li X, Shi J. Polysaccharides from Chinese herbal medicine for anti-diabetes recent advances. Int J Biol Macromol. 2019;121:1240-53.
-
Sabaratnam V, Phan C-W. Neuroactive components of culinary and medicinal mushrooms with potential to mitigate age-related neurodegenerative diseases. In: Discovery and development of neuroprotective agents from natural products. Brahmachari G, editor. Dordrecht (Netherlands): Elsevier; 2018. p. 401-13.
-
Thyagarajan-Sahu A, Lane B, Sliva D. Reishimax, mushroom based dietary supplement, inhibits adipocyte differentiation, stimulates glucose uptake and activates AMPK. BMC Complement Altern Med. 2011;11(1):74.
-
Lu J, He R, Sun P, Zhang F, Linhardt RJ, Zhang A. Molecular mechanisms of bioactive polysaccharides from Ganoderma lucidum (lingzhi), a review. Int J Biol Macromol. 2020;150:765-74.
-
Xin H, Fang L, Xie J, Qi W, Niu Y, Yang F, Cai D, Zhang Y, Wen Z. Identification and quantification of triterpenoids in lingzhi or reishi medicinal mushroom, Ganoderma lucidum Agaricomycetes), with HPLC-MS/MS methods. Int J Med Mushrooms. 2018;20(10):919-34.
-
Abraham TM, Pedley A, Massaro JM, Hoffmann U, Fox CS. Association between visceral and subcutaneous adipose depots and incident cardiovascular disease risk factors. Circulation. 2015;132(17):1639-47.
-
Wang J, Cao B, Zhao H, Feng J. Emerging roles of Ganoderma lucidum in anti-aging. Carbohydr Polym. 2017;8(6):691-707.
-
Bu S, Yuan CY, Xue Q, Chen Y, Cao F. Bilobalide suppresses adipogenesis in 3T3-l1 adipocytes via the AMPK signaling pathway. Molecules. 2019;24(19):1-14.
-
Fullerton MD, Galic S, Marcinko K, Sikkema S, Pulinilkunnil T, Chen ZP, O'Neill HM, Ford RJ, Palanivel R, O'Brien M, Hardie DG, Macaulay SL, Schertzer JD, Dyck JR, van Denderen BJ, Kemp BE, Steinberg GR. Single phosphorylation sites in acc1 and acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med. 2013;19(12):1649-54.
-
Holm C, Osterlund T, Laurell H, Contreras JA. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annu Rev Nutr. 2000;20:365-93.
-
Schinner S, Willenberg H, Krause D, Schott M, Lamounier-Zepter V, Krug A, Ehrhart-Bornstein M, Bornstein S, Scherbaum W. Adipocyte-derived products induce the transcription of the star promoter and stimulate aldosterone and cortisol secretion from adrenocortical cells through the wnt-signaling pathway. Int J Obes. 2007;31(5):864-70.
-
Kong CS, Kim JA, Kim SK. Anti-obesity effect of sulfated glucosamine by AMPK signal pathway in 3T3-l1 adipocytes. Food Chem Toxicol. 2009;47(10):2401-6.
-
Chen Q, Wang T, Li J, Wang S, Qiu F, Yu H, Zhang Y, Wang T. Effects of natural products on fructose-induced nonalcoholic fatty liver disease (NAFLD). Nutrients. 2017;9(2):96.
-
Ahmadian M, Duncan RE, Sul HS. The skinny on fat: Lipolysis and fatty acid utilization in adipocytes. Trends Endocrinol Metab. 2009;20(9):424-8.
-
Lee I, Kim H, Youn U, Kim J, Min B, Jung H, Na M, Hattori M, Bae K. Effect of lanostane triterpenes from the fruiting bodies of Ganoderma lucidum on adipocyte differentiation in 3T3-l1 cells. Planta Med. 2010;76(14):1558-63.
-
Shimojo Y, Kosaka K, Shirasawa T. Effect of Ganoderma lucidum extract on adipocyte differentiation and adiponectin gene expression in the murine pre-adipocyte cell line, 3T3-l1. Phytother Res. 2011;25(2):202-7.
-
Chang CJ, Lin CS, Lu CC, Martel J, Ko YF, Ojcius DM, Tseng SF, Wu TR, Chen YY, Young JD, Lai HC. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun. 2015;6:1-14.
-
Zheng J, Yang B, Yu Y, Chen Q, Huang T, Li D. Ganoderma lucidum polysaccharides exert anti-hyperglycemic effect on streptozotocin-induced diabetic rats through affecting P-cells. Comb Chem High Throughput Screen. 2012;15(7):542-50.
-
Li F, Zhang Y, Zhong Z. Antihyperglycemic effect of Ganoderma lucidum polysaccharides on streptozotocin-induced diabetic mice. Int J Mol Sci. 2011;12(9):6135-45.
-
Huang HY, Korivi M, Yang HT, Huang CC, Chaing YY, Tsai YC. Effect of Pleurotus tuber-regium polysaccharides supplementation on the progression of diabetes complications in obese-diabetic rats. Chin J Physiol. 2014;57(4):198-208.
-
Wang L, Xu N, Zhang J, Zhao H, Lin L, Jia S, Jia L. Antihyperlipidemic and hepatoprotective activities of residue polysaccharide from Cordyceps militaris su-12. Carbohydr Polym. 2015;131:355-62.