Liver steatosis

Liver steatosis is a pathological condition defined by the excessive accumulation of triglycerides within hepatocytes, typically involving more than 5% of the liver weight [1]. It is not a molecular target (such as a receptor or enzyme) but rather a histological hallmark and clinical manifestation of metabolic dysfunction, recently renamed as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) [3][4]. The condition results from an imbalance between fatty acid acquisition (through uptake or de novo lipogenesis) and removal (via mitochondrial oxidation or secretion as very-low-density lipoproteins) [2]. While simple steatosis can be a benign, reversible state, it serves as a critical precursor to more severe liver injury, including inflammation and fibrosis, known as steatohepatitis [5]. Modern drug development focuses on various molecular targets—such as THR-beta, FXR, and GLP-1 receptors—to mitigate this lipid accumulation and prevent the progression to end-stage liver disease [1][6]. Sources: [1] StatPearls, Hepatic Steatosis; [2] NIH/NIDDK, Nonalcoholic Fatty Liver Disease; [3] Journal of Hepatology, MASLD Nomenclature; [4] AASLD Practice Guidance; [5] Nature Reviews Disease Primers, NAFLD; [6] PubMed/NEJM, Resmetirom for NASH.

Other names

Fatty liverSteatosis hepatisHepatic steatosisNon-alcoholic fatty liver (NAFL)Metabolic dysfunction-associated steatotic liver (MASL)

Current therapeutic approaches do not target liver steatosis as a molecule but rather modulate metabolic pathways to reduce fat accumulation. This includes activating the Thyroid hormone receptor beta (THR-β) to increase fatty acid oxidation, stimulating the Farnesoid X receptor (FXR) to regulate bile acid and lipid metabolism, or utilizing GLP-1 receptor agonists to improve systemic insulin sensitivity and reduce de novo lipogenesis [1][2][3].