Molecular Neurobiology Branch, NIH-IRP, NIDA, Baltimore, Maryland, United States of America.
PLoS One. 2013 Sep 4;8(9):e68245. doi: 10.1371/journal.pone.0068245. eCollection 2013.
Brain pathways, including those in hypothalamus and nucleus of the solitary tract, influence food intake, nutrient preferences, metabolism and development of obesity in ways that often differ between males and females. Branched chain amino acids, including leucine, can suppress food intake, alter metabolism and change vulnerability to obesity. The SLC6A15 (v7-3) gene encodes a sodium-dependent transporter of leucine and other branched chain amino acids that is expressed by neurons in hypothalamus and nucleus of the solitary tract. We now report that SLC6A15 knockout attenuates leucine's abilities to reduce both: a) intake of normal chow and b) weight gain produced by access to a high fat diet in gender-selective fashions. We identify SNPs in the human SLC6A15 that are associated with body mass index and insulin resistance in males. These observations in mice and humans support a novel, gender-selective role for brain amino acid compartmentalization mediated by SLC6A15 in diet and obesity-associated phenotypes.
脑通路，包括下丘脑和孤束核中的通路，以男性和女性之间通常不同的方式影响食物摄入、营养偏好、代谢和肥胖的发展。支链氨基酸，包括亮氨酸，可以抑制食物摄入、改变代谢并改变对肥胖的易感性。SLC6A15（v7-3）基因编码亮氨酸和其他支链氨基酸的钠依赖性转运蛋白，由下丘脑和孤束核中的神经元表达。我们现在报告说，SLC6A15 敲除减弱了亮氨酸减少以下两种情况的能力：a）正常饮食的摄入量；b）通过高脂肪饮食获得的体重增加，以性别选择性的方式。我们在人类 SLC6A15 中鉴定出与男性体重指数和胰岛素抵抗相关的 SNP。这些在小鼠和人类中的观察结果支持了由 SLC6A15 介导的脑氨基酸区室化在饮食和肥胖相关表型中的新型性别选择性作用。
