Ergosterol fraction from Agaricus bisporus modulates adipogenesis and skeletal glucose uptake in high fat diet induced obese C57BL/6 mice

The study aimed to optimize a method of extracting ergosterol rich concentrate (ECF) and to evaluate its significant impact on adipogenesis and associated complications in high-fat diet (HFD) induced obese mice.A comparative analysis (soxhlet and ultra sound assisted extraction) was done to obtain the highest yield of ergosterol from Agaricus bisporus. The ECF was evaluated for the biological effect on 3T3-L1 pre-adipocytes in-vitro and in male C57BL/6 mice model in-vivo.Ultra sound assisted extraction method using the solvent n-hexane resulted in highest ergosterol yield. ECF treatment significantly reduced the differentiation and lipid accumulation in pre-adipocyte cells without any cytotoxicity. In-vivo study illustrated beneficial impact on cholesterol metabolism by down regulating the hepatic gene expression of LXR-α, HMG-CoR and up-regulating LDL-R expression. Significant increase in fecal excretion of cholesterol and bile acids have also been observed among the ECF treated animals compared to high fat diet (HFD) fed mice. ECF had an anti-adipogenic activity in-vivo mainly by inhibiting the activity of PPAR-γ, C/EBP-α and SREBP-1c. The results also depicted the improvement of obesity associated insulin resistance by ECF treatment manly via decrease in plasma resistin and up-regulation in skeletal GLUT4 protein expression.Our study illustrated diverse activity of ECF in the therapeutic management of obesity associated metabolic complications mainly by reducing adipogenesis and improving glucose uptake in skeletal muscle in conjunction with improved cholesterol metabolism.