Hepatic ELOVL3 is dispensable for lipid metabolism in mice

Very long-chain fatty acid elongase 3 (ELOVL3) catalyzes the synthesis of C20-C24 fatty acids and is highly expressed in the liver and adipose tissues. The deficiency of Elovl3 exhibits an anti-obesity effect in mice, but the specific role of hepatic ELOVL3 in lipid metabolism remains unclear. Here we demonstrate that hepatic Elovl3 is not required for lipid homeostasis or the pathogenesis of diet-induced obesity and hepatic steatosis. We generated Elovl3 liver-specific knockout mice via Cre/LoxP approach, which maintained normal expression of ELOVL1 or ELOVL7 in the liver. Unexpectedly, the mutant mice did not show significant abnormalities in body weight, liver mass and morphology, liver triglyceride content, or glucose tolerance when fed normal chow or even a low-fat diet.Moreover, deletion of hepatic Elovl3 did not significantly affect body weight gain or hepatic steatosis induced by high-fat diet. Lipidomic analysis revealed that the lipid profiles were not significantly altered by the loss of hepatic Elovl3. Unlike its global knockouts, the mice lacking Elovl3 specifically in liver displayed normal expression of genes involved in hepatic de novo lipogenesis, lipid uptake, or beta-oxidation at the mRNA and protein levels. Collectively, our data indicate that hepatic ELOVL3 is dispensable for metabolic homeostasis or diet-induced meta-bolic disease. ?? 2023 Elsevier Inc. All rights reserved.

Automated summary

This study reveals that hepatic ELOVL3 is not essential for lipid metabolism and does not play a significant role in maintaining lipid homeostasis or the development of obesity and hepatic steatosis. Liver-specific knockout of Elovl3 does not result in abnormalities in body weight, liver mass and morphology, liver triglyceride content, or glucose tolerance under normal or low-fat diet conditions. Moreover, the deletion of hepatic Elovl3 does not significantly affect body weight gain or hepatic steatosis induced by high-fat diet. Lipidomic analysis shows that the loss of hepatic Elovl3 does not cause substantial changes in lipid profiles. Unlike global knockouts, mice lacking Elovl3 specifically in the liver exhibit normal expression of genes involved in hepatic de novo lipogenesis, lipid uptake, or beta-oxidation at the mRNA and protein levels. Overall, our data indicate that hepatic ELOVL3 is dispensable for metabolic homeostasis or diet-induced metabolic disease.