College of Animal Science, South China Agricultural University, Guangzhou, China.
Int J Obes (Lond). 2012 Aug;36(8):1054-61. doi: 10.1038/ijo.2011.221. Epub 2011 Nov 22.
The fat mass and obesity-associated gene (FTO), a crucial gene that affects human obesity and metabolism, has been widely studied in mammals but remains poorly characterized in birds. We aimed to identify variant FTO transcripts in domestic avian species, and to characterize the expression and biological functions of FTO in chickens.
Variant FTO transcripts and their expression in birds were investigated using RACE and real-time quantitative reverse transcriptase-PCR technology. The effects of FTO on glucose metabolism, growth and body composition were determined by fasting and various diet treatments, as well as association analysis in a F₂ resource population. The function of cFTO1 was further studied by overexpression in chick embryo fibroblast (CEF) cells.
Variant FTO transcripts were identified in chicken (cFTO1 to cFTO4), duck (dFTO1, dFTO2 and dFTO4) and goose (gFTO1, gFTO2 and gFTO5). In the chicken, the complete transcript (cFTO1) was predominantly expressed in the leg muscle, pituitary, hypothalamus and cerebellum. Fasting increased both cFTO1 and PGC1α gene expression in the cerebrum, liver, breast muscle and subcutaneous fat, but decreased expression in the pituitary and anterior hypothalamus. In all tested tissues in chickens, a high-glucose diet markedly increased cFTO1 and PGC1α expression. Feeding a high-fat diet increased both cFTO1 and PGC1α expression, except in the pituitary. Overexpression of cFTO1 in CEF cells significantly increased the expression of PGC1α (2.5-fold), STAT3 (2.2-fold) and HL (1.5-fold), a cluster of genes related to energy metabolism. A total of 65 single nucleotide polymorphisms (SNPs) were identified in chicken FTO, and 18 tested SNPs were significantly associated with traits of body weight, body composition and fatness.
These data collectively indicate that FTO is related to glucose metabolism, body weight, fatness and body composition in birds, thus expanding knowledge of FTO function to non-mammalian species.
肥胖相关基因(FTO)是影响人类肥胖和代谢的关键基因,在哺乳动物中得到了广泛研究,但在鸟类中研究甚少。本研究旨在鉴定家禽物种中的 FTO 变体转录本,并研究 FTO 在鸡中的表达和生物学功能。
采用 RACE 和实时定量 RT-PCR 技术研究鸟类中的 FTO 变体转录本及其表达。通过禁食和不同饮食处理以及在 F₂资源群体中的关联分析,确定 FTO 对葡萄糖代谢、生长和体组成的影响。通过在鸡胚成纤维细胞(CEF)中过表达 cFTO1 进一步研究 cFTO1 的功能。
在鸡(cFTO1 至 cFTO4)、鸭(dFTO1、dFTO2 和 dFTO4)和鹅(gFTO1、gFTO2 和 gFTO5)中鉴定出 FTO 变体转录本。在鸡中,完整的转录本(cFTO1)主要在腿部肌肉、垂体、下丘脑和小脑表达。禁食可增加脑中、肝脏、胸肌和皮下脂肪中的 cFTO1 和 PGC1α 基因表达,但降低垂体和下丘脑前部的表达。在鸡的所有测试组织中,高葡萄糖饮食可显著增加 cFTO1 和 PGC1α 的表达。高脂肪饮食增加了 cFTO1 和 PGC1α 的表达,除了垂体。CEF 细胞中 cFTO1 的过表达显著增加了 PGC1α(2.5 倍)、STAT3(2.2 倍)和 HL(1.5 倍)的表达,这是一组与能量代谢相关的基因。在鸡 FTO 中共鉴定出 65 个单核苷酸多态性(SNP),其中 18 个测试 SNP 与体重、体成分和肥胖性状显著相关。
这些数据表明,FTO 与鸟类的葡萄糖代谢、体重、肥胖和体成分有关,从而将 FTO 功能的知识扩展到非哺乳动物物种。