Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Biochim Biophys Acta Mol Basis Dis. 2017 Oct;1863(10 Pt A):2468-2476. doi: 10.1016/j.bbadis.2017.03.018. Epub 2017 Mar 29.
Inactivating mutations in the melanocortin 3 receptor (Mc3r) have been described as causing obesity in mice, but the physiologic effects of MC3R mutations in humans have been less clear. Here we review the MC3R polymorphisms and mutations identified in humans, and the in vitro, murine, and human cohort studies examining their putative effects. Some, but not all, studies suggest that the common human MC3R variant T6K+V81I, as well as several other rare, function-altering mutations, are associated with greater adiposity and hyperleptinemia with altered energy partitioning. In vitro, the T6K+V81I variant appears to decrease MC3R expression and therefore cAMP generation in response to ligand binding. Knockin mouse studies confirm that the T6K+V81I variant increases feeding efficiency and the avidity with which adipocytes derived from bone or adipose tissue stem cells store triglycerides. Other MC3R mutations occur too infrequently in the human population to make definitive conclusions regarding their clinical effects. This article is part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong Tao.
黑素皮质素 3 受体 (Mc3r) 的失活突变已被描述为导致小鼠肥胖，但人类 Mc3r 突变的生理影响尚不清楚。本文综述了人类 Mc3r 多态性和突变，并对其潜在影响的体外、鼠类和人类队列研究进行了综述。一些（但不是全部）研究表明，常见的人类 Mc3r 变体 T6K+V81I 以及其他一些罕见的、功能改变的突变，与更大的肥胖和瘦素血症有关，并伴有能量分配的改变。在体外，T6K+V81I 变体似乎降低了 MC3R 表达，因此降低了配体结合后 cAMP 的生成。基因敲入小鼠研究证实，T6K+V81I 变体增加了进食效率，以及骨或脂肪组织干细胞衍生的脂肪细胞储存甘油三酯的亲和力。其他 Mc3r 突变在人类中发生的频率太低，无法对其临床影响做出明确的结论。本文是一个题为“黑素皮质素受体”的特刊的一部分-由 Ya-Xiong Tao 编辑。
