Lipogenesis
The metabolic process of synthesising fatty acids and triglycerides for fat storage. Lipogenesis is promoted by insulin and high-carbohydrate diets. Reducing lipogenesis through improved glycaemic control and insulin sensitivity is one mechanism by which metabolic peptide drugs contribute to fat reduction.
Technical Context
De novo lipogenesis (DNL): hepatic conversion of excess carbohydrate-derived acetyl-CoA to fatty acids via the enzymes ACC (acetyl-CoA carboxylase) and FAS (fatty acid synthase), regulated by transcription factors SREBP-1c (activated by insulin) and ChREBP (activated by glucose). DNL contributes to hepatic steatosis (fatty liver) in insulin resistance/T2D — the combination of peripheral insulin resistance with hepatic hyperinsulinaemia drives fat synthesis while simultaneously impairing fat oxidation. GLP-1 RAs reduce hepatic lipogenesis through: improved insulin sensitivity (reduced hyperinsulinaemia → reduced SREBP-1c activation), weight loss (reduced substrate availability), and possible direct hepatic effects (GLP-1Rs are expressed on hepatocytes, though the significance of direct hepatic GLP-1R signalling is debated). These anti-steatotic effects underlie the investigation of GLP-1 RAs for NASH treatment.