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

1. 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. 2. 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 ω6:ω3 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. 3. CONCLUSION: Dependent on the Ac:Pr ratio, especially odd‐chain fatty acid formation and insulin sensitivity are differentially affected, indicating the importance of Pr.