Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed the hepatitis B virus and hepatitis C virus as the leading cause of chronic liver disease in most parts of the Western world. MASLD (formerly known as NAFLD) encompasses both simple steatosis and more aggressive metabolic dysfunction-associated steatohepatitis (MASH), which is accompanied by inflammation, fibrosis, and cirrhosis, and ultimately can lead to hepatocellular carcinoma (HCC). There are currently very few approved therapies for MASH. Weight loss strategies such as caloric restriction can ameliorate the harmful metabolic effect of MASH and inhibit HCC; however, it is difficult to implement and maintain in daily life, especially in individuals diagnosed with HCC. In this study, we tested a time-restricted feeding (TRF) nutritional intervention in mouse models of MASH and HCC. We show that TRF abrogated metabolic dysregulation induced by a Western diet without any calorie restriction or weight loss. TRF improved insulin sensitivity and reduced hyperinsulinemia, liver steatosis, inflammation, and fibrosis. Importantly, TRF inhibited liver tumors in two mouse models of obesity-driven HCC. Our data suggest that TRF is likely to be effective in abrogating MASH and HCC and warrant further studies of time-restricted eating in humans with MASH who are at higher risk of developing HCC.
代谢功能障碍相关脂肪性肝病（MASLD）在西方世界大部分地区已超越乙型肝炎病毒和丙型肝炎病毒，成为慢性肝病的主要病因。MASLD（原名非酒精性脂肪性肝病）包括单纯性脂肪变性和更具侵袭性的代谢功能障碍相关脂肪性肝炎（MASH），后者伴随炎症、纤维化和肝硬化，最终可能发展为肝细胞癌（HCC）。目前针对MASH的获批疗法极为有限。热量限制等减重策略虽能改善MASH的有害代谢效应并抑制HCC，但在日常生活中难以实施和维持，尤其对已确诊HCC的患者而言。本研究在MASH和HCC小鼠模型中测试了限时进食（TRF）营养干预方案。结果表明，TRF在不限制热量或减轻体重的情况下，完全阻断了西方饮食诱导的代谢失调。TRF改善了胰岛素敏感性，降低了高胰岛素血症、肝脏脂肪变性、炎症和纤维化程度。重要的是，TRF在两种肥胖驱动型HCC小鼠模型中均抑制了肝脏肿瘤发展。我们的数据表明，TRF可能有效阻断MASH和HCC进展，值得对HCC高风险MASH患者开展限时进食的进一步临床研究。
肿瘤(癌症)患者之家