Metabolic Dysfunction-Associated Steatotic Liver Disease: A Dark Horse of Metabolic Syndrome
Keywords:
Metabolic dysfunction-associated steatotic liver disease, Metabolic syndrome, Cardio-metabolic riskAbstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to obesity, type 2 diabetes mellitus, hypertension, and other cardiometabolic risk factors, with an increased risk of cardiovascular events, chronic kidney disease, hepatic and extrahepatic malignancies, and also liver-related outcomes, including liver failure. The nomenclature MASLD has a long evolution history from 1836 to 2023. The term Non Alcoholic Fatty Liver Disease (NAFLD) used previously did not include cardio-metabolic risk factors as diagnostic criteria. By contrast, MASLD should have at least one of the four defined cardiometabolic risk factors. Insulin resistance is nearly universal in patients with MASLD and is present in the liver, adipose tissue, and muscle. Adipose tissue insulin resistance is characterized by increased release of free fatty acids (FFA) from adipocytes (lipolysis) in the fasting state, which accumulate inside the liver and undergo triglyceride formation. Dietary carbohydrates, in the form of dietary sugars (e.g., fructose, sucrose, and glucose), drive the formation and accumulation of intrahepatic fat from de novo lipogenesis (DNL). This review discusses in depth the pathogenesis of hepatic steatosis and inflammation that may lead to hepatic cellular damage, fibrosis, and cirrhosis. The relationship of MASLD with type-2 diabetes mellitus, hypertension, obesity, and lipid abnormalities is also discussed in detail. In fact, MASLD should be viewed as a hepatic manifestation of metabolic syndrome. There are numerous mechanisms that may accelerate atherosclerosis and premature cardiovascular disease (CVD) in patients with MASLD. So MASLD should not be considered as an isolated disease; rather, it should be viewed as part of a spectrum of disease conditions. Its connectivity with other cardio-metabolic conditions highlights the importance of this dark horse of metabolic disorders.
J MEDICINE 2026; 27(2): 128-135
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