Professor Yang Shufang from Taizhou People’s Hospital Affiliated with Nanjing Medical University states that the liver serves as the core hub regulating energy, glucose, and lipid metabolism in the human body. Energy-dense diets combined with sedentary lifestyles readily trigger obesity, metabolic syndrome (MetS), and type 2 diabetes mellitus (T2DM)—key risk factors for MASLD development. The capacity of adipose tissue and the liver to tolerate and regulate nutritional excess directly determines the onset and progression of MASLD.
When adipose tissue dysfunction occurs, accompanied by insulin resistance (IR) and chronic inflammation, hepatic triglyceride (TG) synthesis increases while oxidative decomposition and transport are impaired, leading to intrahepatic fat accumulation. Multiple adverse factors, including gut microbiota dysbiosis and glucose-lipid toxicity, induce hepatic inflammatory damage by triggering mitochondrial dysfunction, endoplasmic reticulum stress responses, and lipid peroxidation injury. These pathological changes activate hepatic stellate cells, promoting the development of metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma (HCC).
Furthermore, fat accumulation easily causes IR and disrupts glucose-lipid metabolism. Combined with oxidative stress and inflammatory impacts, it exacerbates the pathogenesis of MetS and T2DM, forming a vicious cycle.
The estimated prevalence of MASLD in the general population is approximately 30%, with fluctuations due to individual risk differences. Among T2DM patients, the prevalence of MASLD and its severe subtype—metabolic dysfunction-associated steatohepatitis (MASH)—reaches 55.5% and 37.3%, respectively. Disease burden varies across ethnic groups; surveys indicate Hispanic populations have a 1.36-fold higher risk of MASLD than European whites.
Notably, MASLD can occur even in individuals with normal body weight. Approximately 10% of adults in the United States and 20% in Europe suffer from lean MASLD (non-obese MASLD).