Hepatocyte lipid accumulation pathway

The hepatocyte lipid accumulation pathway refers to the integrated metabolic processes that govern the storage of triglycerides within liver cells. Under physiological conditions, the liver maintains a balance between the acquisition of lipids (via dietary uptake and de novo lipogenesis) and their disposal (via mitochondrial beta-oxidation and secretion as VLDL) [PMID: 33571551]. Dysregulation of this pathway, often driven by insulin resistance and caloric excess, leads to hepatic steatosis, the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD) [PMID: 37863145]. Chronic lipid accumulation can progress to lipotoxicity, oxidative stress, and inflammation, which are key drivers of non-alcoholic steatohepatitis (NASH) and subsequent fibrosis [PMID: 30219650]. Therapeutic strategies targeting this pathway include agonists of thyroid hormone receptor beta (THR-beta) to enhance lipid oxidation and inhibitors of acetyl-CoA carboxylase (ACC) to block lipid synthesis [PMID: 31101479]. Monitoring the activity of this pathway in clinical settings is typically achieved through non-invasive imaging techniques like MRI-PDFF or serum-based biomarkers of liver injury [PMID: 28483163].

Other names

Hepatic steatosis pathwayLiver fat accumulationIntrahepatic triglyceride accumulation

Pharmacological modulation of this pathway involves inhibiting de novo lipogenesis (e.g., via ACC inhibition), enhancing mitochondrial fatty acid beta-oxidation (e.g., via THR-beta agonism), or regulating bile acid and lipid metabolism (e.g., via FXR agonism) [PMID: 33571551, PMID: 31101479].