Cell子刊：脂肪肝是一种昼夜节律疾病，夜间病情加重

Core Insights - The study indicates that Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a diurnal disease influenced by multi-system insulin resistance and reduced insulin availability at night [3][9] - The severity of MASLD and related metabolic disorders exhibits significant diurnal fluctuations, with nighttime being the period of most severe metabolic issues, providing new insights for optimal timing of diet, exercise, and medication for patients [3][12] Summary by Sections - Introduction to MASLD: MASLD affects approximately 40% of the global population and is closely linked to obesity and insulin resistance (IR). It is characterized by excessive triglyceride (TAG) accumulation in liver cells, which can progress to Metabolic Dysfunction-Associated Steatotic Hepatitis (MASH), cirrhosis, and hepatocellular carcinoma [5] - Mechanisms of MASLD: The pathogenesis of MASLD depends on the imbalance between lipid influx and synthesis versus clearance in the liver. TAG in the liver originates from fatty acid esterification, which can come from fat tissue breakdown, dietary intake, or de novo lipogenesis (DNL) [5] - Circadian Influence on Metabolism: Preclinical models show that liver metabolic homeostasis is strongly influenced by biological clocks, which synchronize physiological functions and behaviors over a 24-hour cycle. Disruption of these rhythms can lead to adverse metabolic outcomes, including liver steatosis [6] - Research Findings: The study analyzed diurnal metabolic phenotypes in MASLD patients and overweight controls using advanced stable isotope techniques. Key findings include significant nighttime metabolic dysfunction in MASLD, with activated pathogenic pathways such as hepatic and peripheral insulin resistance, DNL, and systemic NEFA exposure [7][9] - Persistent Nighttime Dysfunction: Even after weight loss and reduction of liver fat, nighttime metabolic dysfunction persists, suggesting it may be a primary driver of steatosis [8] - New Treatment Strategies: The research suggests a new therapeutic approach—time therapy. This includes scheduling most caloric intake during the day when insulin sensitivity is higher, exercising during less favorable metabolic periods, and adjusting medication timing based on the disease's circadian characteristics to maximize efficacy [12]