Urano Tomohiko, Shiraki Masataka, Sasaki Noriko, Ouchi Yasuyoshi, Inoue Satoshi
Departments of Geriatric Medicine (T.U., N.S., Y.O., S.I.) and Anti-Aging Medicine (T.U., N.S., S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; and Research Institute and Practice for Involutional Diseases (M.S.), Nagano 399-8101, Japan.
J Clin Endocrinol Metab. 2015 Apr;100(4):E655-63. doi: 10.1210/jc.2014-2829. Epub 2015 Jan 19.
Genetic factors contribute to the development of obesity.
The aim of this study was to identify novel genes that regulate body fat mass.
We performed a search for single nucleotide polymorphisms (SNPs) associated with body fat percentage using SNP arrays and undertook a replication study and animal study.
Baseline examinations were conducted in 251 (first-stage analysis), 499 (second-stage analysis), and 732 (additional analyses) Japanese postmenopausal women. The mean age (mean ± SD) of the subjects was 66.5 ± 9.4 years. We also analyzed the fat-related phenotypes of a candidate gene in knockout mice.
In the analysis of total body fat, we focused on an SNP of SLC25A24 that showed the lowest significant P value obtained from multiple comparison tests among Japanese postmenopausal women. A significant association was also found between SLC25A24 SNPs and body mass index in the 1482 Japanese postmenopausal women examined in the study. The SLC25A24 SNPs affected the mRNA expression of SLC25A24 in human preadipocytes. Compared with wild-type mice, Slc25a24-KO mice had significantly lower body weights and white adipose tissue weights. Adipocyte differentiation was inhibited in Slc25a24-KO adipose tissues and Slc25a24-knockdown adipocytes.
Genetic analyses in human and mouse models revealed the importance of SLC25A24/Slc25a24 in the regulation of body fat mass and adipogenesis.
遗传因素促成肥胖的发展。
本研究旨在鉴定调控体脂量的新基因。
我们使用单核苷酸多态性（SNP）芯片搜索与体脂百分比相关的单核苷酸多态性，并进行了重复研究和动物研究。
对251名（第一阶段分析）、499名（第二阶段分析）和732名（额外分析）日本绝经后女性进行了基线检查。受试者的平均年龄（均值±标准差）为66.5±9.4岁。我们还分析了基因敲除小鼠中一个候选基因的脂肪相关表型。
在全身脂肪分析中，我们关注SLC25A24的一个单核苷酸多态性，该多态性在日本绝经后女性的多重比较测试中显示出最低的显著P值。在本研究中检查的1482名日本绝经后女性中，还发现SLC25A24单核苷酸多态性与体重指数之间存在显著关联。SLC25A24单核苷酸多态性影响人前脂肪细胞中SLC25A24的mRNA表达。与野生型小鼠相比，Slc25a24基因敲除小鼠的体重和白色脂肪组织重量显著降低。Slc25a24基因敲除的脂肪组织和Slc25a24基因敲低的脂肪细胞中脂肪细胞分化受到抑制。
在人类和小鼠模型中的遗传分析揭示了SLC25A24/Slc25a24在体脂量调节和脂肪生成中的重要性。
