Adipose Tissue Dysfunction in Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is clinically heterogeneous. Patients with similar body mass index, waist circumference, or noninvasive fibrosis stratum may differ markedly in histologic activity, fibrosis trajectory, and progression risk. Adipose tissue dysfunction helps explain this variation. Adipose dysfunction has been characterized by direct depot quantification, measurement of subcutaneous adipose tissue fibrogenesis, adipose tissue insulin resistance, and circulating adipokine profiles. These measures capture different features of adipose biology and have each been linked to liver injury or fibrosis severity. Clinically recognizable body-composition phenotypes—lean MASLD, sarcopenic visceral obesity, myosteatosis, and the hypertriglyceridemic waist—differ in accessibility, mechanistic specificity, and prognostic value. Recent therapeutic developments in metabolic dysfunction-associated steatohepatitis (MASH), including resmetirom, semaglutide, tirzepatide, fibroblast growth factor 21 (FGF21) analogs, and older adipose-directed agents such as pioglitazone, illustrate the importance of distinguishing adipose-mediated, weight-mediated, and liver-directed mechanisms. This review summarizes the literature on adipose tissue dysfunction in MASLD, the body-composition phenotypes associated with it, and recent therapeutic data in the context of adipose–liver–muscle biology.