Hepatic lipid accumulation (Steatosis)

Hepatic lipid accumulation, commonly known as steatosis, is a pathological state characterized by the abnormal retention of lipids, primarily triglycerides, within the cytoplasm of hepatocytes (StatPearls, 2023). This condition occurs when the rate of hepatic lipid acquisition through fatty acid uptake and de novo lipogenesis exceeds the rate of lipid disposal via mitochondrial beta-oxidation and the export of very-low-density lipoproteins (VLDL) (NIH, 2021). It is the defining histological feature of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly referred to as Nonalcoholic Fatty Liver Disease (NAFLD). While hepatic lipid accumulation is often the initial stage of liver disease, it can trigger secondary hits such as oxidative stress and endoplasmic reticulum stress, leading to chronic inflammation and cellular injury (Nature Reviews Disease Primers, 2021). Pharmacological treatments do not target the "accumulation" as a molecule but rather modulate specific receptors and enzymes—such as THR-beta, FXR, or ACC—to restore metabolic balance. Reducing hepatic fat content is a primary clinical endpoint in trials for metabolic liver diseases to prevent progression to steatohepatitis, fibrosis, and cirrhosis.

Other names

Hepatic steatosisFatty liverMacrovesicular steatosisMicrovesicular steatosisIntracellular lipid accumulation

Reduction of hepatic lipid levels by activating thyroid hormone receptor beta (THR-beta), activating farnesoid X receptor (FXR), increasing insulin sensitivity via PPAR-gamma, or modulating incretin receptors (GLP-1R/GIPR) to reduce de novo lipogenesis and enhance fatty acid oxidation.