Impaired mitochondrial medium-chain fatty acid oxidation drives periportal macrovesicular steatosis in sirtuin-5 knockout mice.

ABSTRACT: Medium-chain triglycerides (MCT), containing C₈-C₁₂ fatty acids, are used to treat several pediatric disorders and are widely consumed as a nutritional supplement. Here, we investigated the role of the sirtuin deacylase Sirt5 in MCT metabolism by feeding Sirt5 knockout mice (Sirt5KO) high-fat diets containing either C₈/C₁₀ fatty acids or coconut oil, which is rich in C₁₂, for five weeks. Coconut oil, but not C₈/C₁₀ feeding, induced periportal macrovesicular steatosis in Sirt5KO mice. ¹⁴C-C₁₂ degradation was significantly reduced in Sirt5KO liver. This decrease was localized to the mitochondrial β-oxidation pathway, as Sirt5KO mice exhibited no change in peroxisomal C₁₂ β-oxidation.

SUBMITTER: Goetzman ES 

PROVIDER: S-EPMC7591893 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature