The Medicinal Mushroom Ganoderma neo-japonicum (Agaricomycetes) Polysaccharide Extract Prevents Obesity-Induced Diabetes in C57BL/6J Mice

<i>Ganoderma neo-japonicum</i> Imazeki is a medicinal mushroom consumed by the indigenous people in Malaysia as a remedy for diabetes. This study aims to validate the efficacy of <i>G. neo-japonicum</i> polysaccharides (GNJP) on obesity-induced type 2 diabetes mellitus (T2DM) in C57BL/6J mice. Mice were divided into seven groups; normal diet (ND)-control, high-fat-diet (HFD)-control, HFDGNJP-treated (50, 100, 200 mg/kg b.w.), HFDMET (metformin 50 mg/kg; positive-control) and ND-GNJP (200 mg/kg b.w.). Mice were administered GNJP or metformin orally for 10 weeks (thrice/week) and sacrificed after an oral glucose tolerance test. Body weight, serum biochemicals, liver histology, adipocyte gene expressions, glucose and insulin levels were measured. HFD caused obesity, dyslipidemia, and diabetes in the untreated groups. GNJP (50 mg/kg b.w.) supplementation prevented weight gain and liver steatosis, improved serum lipid profile and glucose tolerance and attenuated hyperglycemia and hyperinsulinemia more effectively when compared with the other treatment groups. The prevention of obesity and lipid dysregulation is plausibly attributed to the increased hormone-sensitive lipase and reduced <i>Akt-1</i> and <i>Ppary</i> gene expressions while the up-regulation of <i>AdipoQ</i> (adiponectin), <i>Prkag2</i> and <i>Slc2a4</i> genes served to sensitize insulin and improve glucose uptake. Thus, supplementation with an appropriate dose of GNJP has promising efficacies in preventing HFD aka obesity-induced T2DM and associated metabolic abnormalities.