非酒精性脂肪肝
CD36
内科学
内分泌学
脂肪变性
脂肪生成
生物
脂肪肝
人口
胰岛素抵抗
肥胖
疾病
医学
脂质代谢
环境卫生
受体
作者
Aline de Conti,Volodymyr Tryndyak,Rose Willett,Barbara Borowa-Mazgaj,Anna Watson,Ralph E. Patton,Sangeeta Khare,Levan Muskhelishvili,Greg R. Olson,Mark Avigan,Carl E. Cerniglia,Sharon A. Ross,Arun J. Sanyal,Frederick A. Beland,Ivan Rusyn,Igor P. Pogribny
标识
DOI:10.1096/fj.202000194r
摘要
Interindividual variability and sexual dimorphisms in the development of nonalcoholic fatty liver disease (NAFLD) are still poorly understood. In the present study, male and female strains of Collaborative Cross (CC) mice were fed a high-fat and high-sucrose (HF/HS) diet or a control diet for 12 weeks to investigate interindividual- and sex-specific variations in the development of NAFLD. The severity of liver steatosis varied between sexes and individual strains and was accompanied by an elevation of serum markers of insulin resistance, including increases in total cholesterol, low-density lipoproteins, high-density lipoproteins, phospholipids, and glucose. The development of NAFLD was associated with overexpression of the critical fatty acid uptake and de novo lipogenesis genes Pparg, Mogat1, Cd36, Acaab1, Fabp2, and Gdf15 in male and female mice. The expression of Pparg, Mogat1, and Cd36 was positively correlated with liver triglycerides in male mice, and Mogat1 and Cd36 expression were positively correlated with liver triglycerides in female mice. Our results indicate the value of CC mice in combination with HF/HS diet-induced alterations as an approach to study the susceptibility and interindividual variabilities in the pathogenesis of nonalcoholic fatty liver and early nonalcoholic steatohepatitis at the population level, uncovering of susceptible and resistant cohorts, and identifying sex-specific molecular determinants of disease susceptibility.
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