Hepatic triglyceride accumulation

Hepatic triglyceride accumulation, scientifically known as hepatic steatosis, is a pathological state characterized by the excessive buildup of lipids, primarily triglycerides, within the cytoplasm of hepatocytes. This condition arises from an imbalance between lipid acquisition (uptake of circulating fatty acids and de novo lipogenesis) and lipid disposal (fatty acid oxidation and secretion of very-low-density lipoproteins). It is the defining feature of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD), and serves as a precursor to more severe conditions like Metabolic Dysfunction-Associated Steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma (PMID: 32514332, 37305141). While 'Hepatic triglyceride accumulation' is a clinical phenotype rather than a single molecular target, it is the primary therapeutic endpoint for a wide range of drug classes. Pharmacological strategies to reduce liver fat include targeting specific enzymes like Acetyl-CoA carboxylase (ACC) and Diacylglycerol O-acyltransferase 2 (DGAT2), or nuclear receptors such as Thyroid Hormone Receptor-beta (THR-β) and Farnesoid X Receptor (FXR). Recent breakthroughs, such as the approval of Resmetirom, demonstrate that reducing hepatic fat content is a critical step in resolving liver inflammation and preventing the progression of metabolic liver diseases (PMID: 38330338).

Other names

Hepatic steatosisFatty liverIntrahepatic lipid accumulationLiver fat accumulationSteatosis hepatis

Hepatic triglyceride accumulation is reduced by various mechanisms including the inhibition of de novo lipogenesis (via ACC or DGAT2 inhibitors), the enhancement of mitochondrial fatty acid oxidation (via THR-beta agonists), the reduction of fatty acid delivery from adipose tissue (via GLP-1/GIP agonists), and the modulation of bile acid pathways (via FXR agonists).