Although regularly associated with obesity, non-alcoholic fatty liver disease (NAFLD) is increasingly identified in patients with normal body mass index. Compared with obese individuals with NAFLD, lean individuals with NAFLD have a lower prevalence of diabetes, hypertension, hypertriglyceridemia and metabolic syndrome, but higher fibrosis scores and cardiovascular morbidity. New studies with relevant experimental models are needed to understand the mechanisms leading to cardiac abnormalities in this population and guide the development of therapies. Using a genetic mouse model of lean-NAFLD, a new study demonstrates differences in the progression of lean NAFLD and cardiovascular complications between female and male mice. Lrpprc knockout (KO) mice, known for developing mitochondrial hepatopathy in the absence of obesity, showed hepatic structural damage and hepatocellular injury independently of sexes. However, KO males showed a more severe phenotype when considering hepatic inflammation, alterations in glucose metabolism and cardiac diastolic function.

Original reference: Burelle, C. et al. Commun. Biol. 7, 356 (2024)

尽管非酒精性脂肪肝 (NAFLD) 通常与肥胖相关，但在体重指数正常的患者中越来越多地发现这种疾病。与患有NAFLD的肥胖个体相比，患有NAFLD的瘦个体的糖尿病、高血压、高甘油三酯血症和代谢综合征的患病率较低，但纤维化评分和心血管发病率较高。需要利用相关实验模型进行新的研究，以了解导致该人群心脏异常的机制并指导治疗的开发。一项新的研究使用瘦型 NAFLD 基因小鼠模型，证明了雌性和雄性小鼠之间瘦型 NAFLD 进展和心血管并发症的差异。Lrpprc基因敲除 (KO) 小鼠因在没有肥胖的情况下发生线粒体肝病而闻名，它们表现出与性别无关的肝结构损伤和肝细胞损伤。然而，考虑到肝脏炎症、葡萄糖代谢和心脏舒张功能的改变，KO 雄性表现出更严重的表型。

原始参考文献： Burelle, C. 等人。交流。生物。7 , 356 (2024)