Parikh Dippal, Jayakumar Smitha, Oliveira-Paula Gustavo H, Almonte Vanessa, Riascos-Bernal Dario F, Sibinga Nicholas E S
Department of Medicine (Cardiology), and Department of Developmental and Molecular Biology, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
iScience. 2022 Sep 3;25(10):105058. doi: 10.1016/j.isci.2022.105058. eCollection 2022 Oct 21.
Mouse models enable the study of genetic factors affecting the complex pathophysiology of metabolic disorders. Here, we identify reductions in leptin levels, food intake, and obesity due to high-fat diet, accompanied by increased leptin sensitivity, in mice that harbor the E2a-Cre transgene within , an obesity quantitative trait locus (QTL) that includes the leptin gene. Interestingly, loss of allograft inflammatory factor-1-like (AIF1L) protein in these transgenic mice leads to similar leptin sensitivity, yet marked reversal of the obesity phenotype, with accelerated weight gain and increased food intake. Transgenic mice lacking AIF1L also have low circulating leptin, which suggests that benefits of enhanced leptin sensitivity are lost with further impairment of leptin expression due to loss of AIF1L. Together, our results identify AIF1L as a genetic modifier of and leptin that affects leptin levels, food intake, and obesity during the metabolic stress imposed by HFD.
小鼠模型有助于研究影响代谢紊乱复杂病理生理学的遗传因素。在此，我们发现，在一个包含瘦素基因的肥胖数量性状位点（QTL）内携带E2a-Cre转基因的小鼠中，由于高脂饮食导致瘦素水平降低、食物摄入量减少和肥胖，同时伴有瘦素敏感性增加。有趣的是，这些转基因小鼠中同种异体移植炎症因子-1样（AIF1L）蛋白的缺失导致了类似的瘦素敏感性，但肥胖表型明显逆转，体重增加加速且食物摄入量增加。缺乏AIF1L的转基因小鼠循环瘦素水平也较低，这表明由于AIF1L的缺失导致瘦素表达进一步受损，增强的瘦素敏感性带来的益处丧失。总之，我们的结果确定AIF1L是一个影响瘦素水平、食物摄入量以及在高脂饮食施加的代谢应激期间肥胖的 和瘦素的遗传修饰因子。
