Modulation of obesity associated metabolic dysfunction by novel lipophilic fraction obtained from Agaricus bisporus.

The present study aimed to prepare a novel lipophilic fraction rich in fat soluble bioactive from Agaricus bisporus and investigated its impact through in vitro and in vivo assessments since the prospective biological activities of fat soluble components from mushrooms are limited. Ergosterol concentrate fraction (ECF) preparation followed by subsequent characterization of the extract using various analytical techniques (HPLC-UV, Mass spectroscopy, NMR). Furthermore, the fraction has been evaluated for antioxidant activity, DNA protection ability, hypolipidemic properties by in vitro specific enzyme inhibition and in vivo animal model (C57BL/6). The fraction majorly contains ergosterol (504 mg/100 g dw) and linoleic acid (71.92 %). In vitro studies showed that the fraction limited free radicals induced DNA damage, exhibited significant free radical scavenging activities (IC 50 of DPPH 15.64; ABTS 8.28 mg/ml), and inhibited HMG-CoA reductase activity (IC 50 5.03 mg/ml). Further, in vivo study showed that ECF treatment significantly (p < 0.05) improved insulin sensitivity (reduced plasma glucose & insulin, increased adiponectin) and reduced inflammatory markers (CRP & TNF-α) in comparison to high fat fed mice. Furthermore, ECF has significantly reduced plasma lipid profile and accumulation of lipids in liver. This could be due to down regulation of mRNA expression of lipogenic transcription factors such as SREBP-1c and SREBP-2, and key lipogenic enzyme ACC. Moreover, ECF treatment has suppressed protein expression of FAS, induced cholesterol clearance by enhancing LDL-R protein expression. The present work for the first time evaluated the synergistic potential of ergosterol and linoleic acid to improve antioxidant defense system and ameliorate obesity associated metabolic dysfunction. [Display omitted] • A novel ergosterol concentrate fraction (ECF) prepared from Agaricus bisporus by a simple non conventional technique enriched in ergosterol and linoleic acid. • In vitro ; ECF exhibited free radical scavenging activity, limited free radical induced DNA damage and inhibited HMG-CoA reductase activity. • In-vivo; ECF improved insulin sensitivity, glucose homeostasis and increased anti inflammatory adipokine (adiponectin) in C57BL/6 mice. • ECF down regulated hepatic gene expression of transcription factors SREBP-1c, SREBP-2 and key lipogenic enzyme ACC. • ECF suppressed protein expression of FAS, induced cholesterol clearance by enhancing LDL-R protein expression. [ABSTRACT FROM AUTHOR]