Propionate Promotes Intestinal Lipolysis and Metabolic Benefits via AMPK/LSD1 Pathway in Mice

: Dietary fibers and their microbial fermentation products short chain fatty acids promote metabolic benefits, but the underlying mechanisms are still unclear. Recent studies indicate that intestinal lipid handling is under regulatory control and has broad influence on whole body energy homeostasis. Here we reported that dietary inulin and propionate significantly decreased whole body fat mass without affecting food intake in mice fed with chow diet. Meanwhile, triglyceride (TG) content was decreased and lipolysis genes expressions, such as adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL) and lysosomal acid lipase (LAL) were 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 expressions and decreased TG content, via activation of phosphorylation of AMP-activated protein kinase (p-AMPK) and lysine specific demethylase 1 (LSD1). Moreover, inulin and propionate could increase intestinal lipolysis under high fat diet (HFD) fed condition which contributed to the prevention of HFD-induced obesity. Our study suggests dietary fiber inulin and its microbial fermentation product propionate can regulate metabolic homeostasis through regulating intestinal lipid handling, which could provide a novel therapeutic target for both prevention and treatment of obesity.