Veterinary Research Centre, Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 100, 02-797, Warsaw, Poland.
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, 02-106, Warsaw, Poland.
Sci Rep. 2020 Aug 3;10(1):13029. doi: 10.1038/s41598-020-69856-5.
Genome-wide association studies in the FTO gene have identified SNPs correlating with obesity and type 2 diabetes. In mice, lack of Fto function leads to intrauterine growth retardation and lean phenotype, whereas in human it is lethal. The aim of this study in a pig model was to determine the localization of the FTO protein in different tissues and cell compartments, in order to investigate potential targets of FTO action. To better understand physiological role of FTO protein, its expression was studied in pigs of different age, metabolic status and nutrition, using both microscopic methods and Western blot analysis. For the first time, FTO protein was found in vivo in the cytoplasm, of not all, but specific tissues and cells e.g. in the pancreatic β-cells. Abundant FTO protein expression was found in the cerebellum, salivary gland and kidney of adult pigs. No FTO protein expression was detected in blood, saliva, and bile, excluding its role in cell-to-cell communication. In the pancreas, FTO protein expression was positively associated with energy intake, whereas in the muscles it was strictly age-related. In IUGR piglets, FTO protein expression was much higher in the cerebellum and kidneys, as compared to normal birth body weight littermates. In conclusion, our data suggest that FTO protein may play a number of distinct, yet unknown intracellular functions due to its localization. Moreover, it may play a role in animal growth/development and metabolic state, although additional studies are necessary to clarify the detailed mechanism(s) of action.
全基因组关联研究发现 FTO 基因中的 SNP 与肥胖和 2 型糖尿病相关。在小鼠中，Fto 功能缺失导致宫内生长迟缓和瘦表型，而在人类中则是致命的。本研究在猪模型中的目的是确定 FTO 蛋白在不同组织和细胞区室中的定位，以研究 FTO 作用的潜在靶点。为了更好地理解 FTO 蛋白的生理作用，使用显微镜方法和 Western blot 分析研究了不同年龄、代谢状态和营养状况的猪中 FTO 蛋白的表达。首次在体内发现 FTO 蛋白存在于细胞质中，而不是所有组织和细胞中，例如在胰腺β细胞中。在成年猪的小脑、唾液腺和肾脏中发现大量的 FTO 蛋白表达。在血液、唾液和胆汁中未检测到 FTO 蛋白表达，排除了其在细胞间通讯中的作用。在胰腺中，FTO 蛋白表达与能量摄入呈正相关，而在肌肉中则与年龄严格相关。在 IUGR 仔猪中，小脑和肾脏中的 FTO 蛋白表达明显高于正常出生体重的同窝仔猪。总之，我们的数据表明，由于 FTO 蛋白的定位，它可能发挥许多不同的、但未知的细胞内功能。此外，它可能在动物生长/发育和代谢状态中发挥作用，尽管需要进一步研究来阐明其详细的作用机制。
