Elevation of hepatic de novo lipogenesis in mice with overnutrition is dependent on multiple substrates.

ABSTRACT: Increased de novo lipogenesis (DNL) contributes to hyperlipidemia, MASLD, and ASCVD in insulin-resistant subjects. However, multiple pathways support lipogenesis and few have sought to quantify the contributions of the discrete metabolic pathways that contribute to lipogenesis. In this study, antisense oligonucleotides (ASOs) targeting glucokinase (Gck), lactate dehydrogenase A (Ldha), and glutamic-pyruvic transaminase 2 (Gpt2) were utilized to restrict substrate flux from lipogenic precursors in C57BL6/J mice, comparing controls (CO) and chronic overnutrition (ON). In CO mice, ASO treatments did not significantly alter lipogenesis; however, there was a trend toward decreased hepatic triglyceride content and DNL, especially with the GPT2 ASO (TG = -46.8%; DNL = -53.7%). Expectedly, increas

SUBMITTER: Strober JW 

PROVIDER: S-EPMC12268660 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature