Tricaprylin, a medium-chain triglyceride, aggravates high-fat diet-induced fat deposition but improves intestinal health

Medium-chain triglycerides (MCTs) are absorbed and metabolized more rapidly than long-chain triglycerides (LCTs) and therefore are considered to have obesity-prevention potential in foods. The effect of adding tricaprylin, an MCT, to food on fat deposition and intestinal health is uncharted. In this study, mice were randomly divided into four groups and fed a normal diet (ND), ND with tricaprylin, a high-fat diet (HFD), or HFD with tricaprylin. Supplementation of 2% tricaprylin in HFD significantly increased the body weight, fat mass, liver weight, adipocyte size in adipose tissue and liver, and upregulated genes related to fat deposition. Metabolomic analysis of serum and adipose tissue revealed that tricaprylin significantly increased the contents of metabolites related to lipid metabolism, triglyceride storage, and fat deposition related signaling pathways. In vitro experiments and molecular docking analysis suggest that octanoic acid, a primary decomposition product of tricaprylin, may promote adipogenic differentiation of preadipocytes by acting as a PPARγ ligand to activate the expression of lipogenesis-related genes. Although supplementation with 2% tricaprylin in HFD cannot reduce fat deposition, it has a beneficial effect on intestinal health. Tricaprylin improved intestinal morphology, digestive enzyme activity, short-chain fatty acid concentration, and intestinal barrier function-related protein expression, while reducing inflammatory factor levels and the abundance of harmful intestinal microorganisms.