Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high-fat diet-induced obesity

Scope: The SCFA acetate (Ac) and propionate (Pr) are major fermentation products of dietary fibers and provide additional energy to the host. We investigated short-and long-term effects of dietary Ac and Pr supplementation on diet-induced obesity and hepatic lipid metabolism. Methods and results: C3H/HeOuJ mice received high-fat (HF) diets supplemented with 5% SCFA in different Ac: Pr ratios, a high acetate (HF-HAc; 2.5:1 Ac: Pr) or high Pr ratio (HF-HPr; 1: 2.5 Ac: Pr) for 6 or 22 weeks. Control diets (low-fat (LF), HF) contained no SCFA. SCFA did not affect body composition but reduced hepatic gene and protein expression of lipogenic enzymes leading to a reduced hepatic triglyceride concentration after 22 weeks in HF-HPr mice. Analysis of long-chain fatty acid composition (liver and plasma phospholipids) showed that supplementation of both ratios led to a lower omega 6:omega 3 ratio. Pr directly led to increased odd-chain fatty acid (C15:0, C17:0) formation as confirmed in vitro using HepG2 cells. Remarkably, plasma C15:0 was correlated with the attenuation of HF diet-induced insulin resistance. Conclusion: Dependent on the Ac: Pr ratio, especially odd-chain fatty acid formation and insulin sensitivity are differentially affected, indicating the importance of Pr.