Hepatic lipogenic and fatty acid oxidation pathways (DNL/FAO pathways)

Hepatic lipogenic and fatty acid oxidation pathways are the central metabolic processes regulating lipid homeostasis in the liver. De novo lipogenesis (DNL) involves the enzymatic conversion of acetyl-CoA into fatty acids, primarily regulated by enzymes like Acetyl-CoA Carboxylase (ACC) and Fatty Acid Synthase (FASN) (Source: NIH/NCBI, De Novo Lipogenesis in Health and Disease). Conversely, fatty acid oxidation, or beta-oxidation, occurs in the mitochondria and breaks down fatty acids to generate ATP, a process often regulated by Peroxisome Proliferator-Activated Receptor alpha (PPAR-alpha) (Source: StatPearls, Fatty Acid Oxidation). Dysregulation of these pathways, characterized by excessive DNL and impaired oxidation, is a primary driver of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Non-Alcoholic Steatohepatitis (NASH) (Source: Nature Reviews Gastroenterology & Hepatology). Therapeutic strategies target these pathways using inhibitors of lipogenic enzymes or agonists of nuclear receptors like Thyroid Hormone Receptor beta (THR-beta) to reduce hepatic fat accumulation (Source: New England Journal of Medicine, Resmetirom for NASH). While promising, targeting these pathways requires careful monitoring of systemic lipid levels, as some ACC inhibitors have been associated with paradoxical increases in serum triglycerides (Source: Journal of Hepatology).

Other names

Hepatic lipid metabolismDe novo lipogenesis and beta-oxidationLiver fatty acid metabolismHepatic lipid flux

Modulation of lipid flux through the inhibition of rate-limiting lipogenic enzymes (e.g., ACC, FASN) or the activation of transcriptional regulators (e.g., PPAR-alpha, THR-beta) that promote fatty acid catabolism.