Resinacein S, a novel triterpenoid from functional mushroom Ganoderma resinaceum, curbs obesity by regulating thermogenesis and energy metabolism.

Ganoderma mushrooms are popularly used as dietary supplements to promote health around the world. However, their potential applications for the prevention and treatment of obesity needs to be further investigated. In this study, we isolated a novel triterpenoid from Ganoderma resinaceum, Resinacein S (Res S), and determined its absolute configuration. We reported that Res S treatment significantly inhibited the high-fat HF diet-induced body weight gain though increased thermogenesis and energy metabolism. Specifically, treatment with Res S promoted brown adipose tissue activation and browning of inguinal white adipose tissue, improving whole-body glucose and lipid homeostasis. Mechanistically, Res S treatment induced the expression of thermogenic genes and related protein, for example, uncoupling protein 1 and mitochondrial biogenesis in a cell-autonomous manner by activating the AMPK-PGC1α signaling pathway. These findings identify Res S as a potential therapeutic alternative for obesity in the setting of its increasingly high prevalence. HIGHLIGHTS: Resinacein S (Res S) exhibited potent anti-obesity effects in high-fat diet-fed mice; Res S treatment significantly promoted brown adipose tissue activation and browning of inguinal white adipose tissue; Res S treatment stimulated UCP1 expression and enhanced mitochondrial function; Res S induced adipocyte thermogenic activity through activating the AMPK-PGC1α axis.