Propionate promotes intestinal lipolysis and metabolic benefits via AMPK/LSD1 pathway in mice

Abstract

Dietary fibers and their microbial fermentation products short-c hain fatty acids promote metabolic benefits, but the underlying mechanisms are st ill unclear. Recent studies indicate that intestinal lipid handling is under regulatory control and has broad influence on whole body energy homeostasis. Here we reported tha t dietary inulin and propionate significantly decreased whole body fat mass without a ffecting food intake in mice fed with chow diet. Meanwhile, triglyceride (TG) content was decreased and lipolysis gene expression, such as adipose triglyceride lipase (Atgl), hormone-sensitive lipase (Hsl) and lysosomal acid lipase (Lal) was elevated in the jejunum and ileum of inulin- and propionate-treated mice. In vitro studies on Caco-2 cells showed propionate directly induced enterocyte Atgl, Hsl and Lal gene expression and decreased TG content, via activation of phosphorylation of AMP-activated protein kina se (p-AMPK) and lysine-specific demethylase 1 (LSD1). Moreover, inulin and propi onate could increase intestinal lipolysis under high-fat diet (HFD)-fed condition which contributed to the prevention of HFD-induced obesity. Our study suggests that diet ary fiber inulin and its microbial fermentation product propionate can regulate metabolic homeostasis through regulating intestinal lipid handling, which may provide a novel therapeutic target for both prevention and treatment of obesity.