Albert Einstein College of Medicine, Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), and Department of Developmental and Molecular Biology. 1300 Morris Park Avenue, Bronx, New York, 10461, USA.
Diabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Langone Medical Center, New York, NY, 10016, USA.
Sci Rep. 2020 Feb 27;10(1):3594. doi: 10.1038/s41598-020-60433-4.
The allograft inflammatory factor (AIF) gene family consists of two identified paralogs - AIF1 and AIF1-like (AIF1L). The encoded proteins, AIF1 and AIF1L, are 80% similar in sequence and show conserved tertiary structure. While studies in human populations suggest links between AIF1 and metabolic diseases such as obesity and diabetes, such associations with AIF1L have not been reported. Drawing parallels based on structural similarity, we postulated that AIF1L might contribute to metabolic disorders, and studied it using mouse models. Here we report that AIF1L is expressed in major adipose depots and kidney but was not detectable in liver or skeletal muscle; in notable contrast to AIF1, AIF1L was also not found in spleen. Studies of AIF1L deficient mice showed no obvious postnatal developmental phenotype. In response to high fat diet (HFD) feeding for 6 or 18 weeks, WT and AIF1L deficient mice gained weight similarly, showed no differences in fat or lean mass accumulation, and displayed no changes in energy expenditure or systemic glucose handling. These findings indicate that AIF1L is not essential for the development of obesity or impaired glucose handling due to HFD, and advance understanding of this little-studied gene and its place in the AIF gene family.
同种异体炎症因子 (AIF) 基因家族由两个已鉴定的直系同源物 - AIF1 和 AIF1 样 (AIF1L) 组成。编码的蛋白质 AIF1 和 AIF1L 在序列上有 80%的相似性，并且表现出保守的三级结构。虽然在人类群体中的研究表明 AIF1 与肥胖和糖尿病等代谢疾病之间存在联系，但尚未报道与 AIF1L 有这种关联。基于结构相似性进行推断，我们假设 AIF1L 可能与代谢紊乱有关，并使用小鼠模型进行了研究。在这里，我们报告 AIF1L 在主要脂肪组织和肾脏中表达，但在肝脏或骨骼肌中检测不到；与 AIF1 形成鲜明对比的是，AIF1L 也不在脾脏中发现。AIF1L 缺失小鼠的研究表明，其出生后没有明显的发育表型。在高脂肪饮食 (HFD) 喂养 6 或 18 周后，WT 和 AIF1L 缺失小鼠的体重增加相似，脂肪或瘦体重积累没有差异，能量消耗或全身葡萄糖处理也没有变化。这些发现表明，AIF1L 对于由于 HFD 引起的肥胖或葡萄糖处理受损的发展不是必需的，并且加深了对这个研究较少的基因及其在 AIF 基因家族中的地位的理解。
