A MicroRNA Linking Human Positive Selection and Metabolic Disorders.
A MicroRNA Linking Human Positive Selection and Metabolic Disorders.
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DOI：
10.1016/j.cell.2020.09.017
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发表时间：
2020-10-29
期刊：
影响因子：
64.5
通讯作者：
Näär AM
中科院分区：
文献类型：
--
作者：
Wang L;Sinnott-Armstrong N;Wagschal A;Wark AR;Camporez JP;Perry RJ;Ji F;Sohn Y;Oh J;Wu S;Chery J;Moud BN;Saadat A;Dankel SN;Mellgren G;Tallapragada DSP;Strobel SM;Lee MJ;Tewhey R;Sabeti PC;Schaefer A;Petri A;Kauppinen S;Chung RT;Soukas A;Avruch J;Fried SK;Hauner H;Sadreyev RI;Shulman GI;Claussnitzer M;Näär AM
欧洲人在2q21.3位点上的正选择携带乳糖酶基因，被认为是选择成年人消化牛奶的能力，以在古代的饥荒中生存下来。然而，2q21.3基因座也与人类的肥胖和2型糖尿病有关，这增加了该基因座中的其他遗传因素可能通过促进能量储存而促进了对饥荒的进化适应，但现在却赋予了对代谢疾病的易感性。我们在这里表明，位于正选择位点中心的miR-128-1 microRNA代表了哺乳动物中至关重要的代谢调节因子。在小鼠代谢性疾病模型中，miR-128-1的反义靶向和基因消除导致能量消耗增加和高脂饮食诱导的肥胖的改善，以及显著改善的葡萄糖耐量。与miR-128-1依赖性能量储存相关的节俭表型可能将古代适应与饥饿和与营养过剩相关的现代代谢适应不良联系起来。与古代对牛奶消费的适应有关的正选择位点也与代谢紊乱有关，并且包含控制能量消耗的microRNA，可能将这两种表型和选择在代谢疾病中的作用联系起来。
Positive selection in Europeans at the 2q21.3 locus harboring the lactase gene has been attributed to selection for the ability of adults to digest milk to survive famine in ancient times. However, the 2q21.3 locus is also associated with obesity and type 2 diabetes in humans, raising the possibility that additional genetic elements in the locus may have contributed to evolutionary adaptation to famine by promoting energy storage, but which now confer susceptibility to metabolic diseases. We show here that the miR-128-1 microRNA, located at the center of the positively selected locus, represents a crucial metabolic regulator in mammals. Antisense targeting and genetic ablation of miR-128-1 in mouse metabolic disease models result in increased energy expenditure and amelioration of high fat diet-induced obesity, and markedly improved glucose tolerance. A thrifty phenotype connected to miR-128-1-dependent energy storage may link ancient adaptation to famine and modern metabolic maladaptation associated with nutritional overabundance. A positively selected locus linked to ancient adaptation to milk consumption is also linked to metabolic disorders and contains a microRNA that controls energy expenditure, potentially connecting these two phenotypes and the role of selection in metabolic disease.
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影响因子：
4.5
作者：
Heard-Costa NL;Zillikens MC;Monda KL;Johansson A;Harris TB;Fu M;Haritunians T;Feitosa MF;Aspelund T;Eiriksdottir G;Garcia M;Launer LJ;Smith AV;Mitchell BD;McArdle PF;Shuldiner AR;Bielinski SJ;Boerwinkle E;Brancati F;Demerath EW;Pankow JS;Arnold AM;Chen YD;Glazer NL;McKnight B;Psaty BM;Rotter JI;Amin N;Campbell H;Gyllensten U;Pattaro C;Pramstaller PP;Rudan I;Struchalin M;Vitart V;Gao X;Kraja A;Province MA;Zhang Q;Atwood LD;Dupuis J;Hirschhorn JN;Jaquish CE;O'Donnell CJ;Vasan RS;White CC;Aulchenko YS;Estrada K;Hofman A;Rivadeneira F;Uitterlinden AG;Witteman JC;Oostra BA;Kaplan RC;Gudnason V;O'Connell JR;Borecki IB;van Duijn CM;Cupples LA;Fox CS;North KE
通讯作者：
North KE
影响因子：
4.4
作者：
Barendse W;Harrison BE;Bunch RJ;Thomas MB;Turner LB
通讯作者：
Turner LB
影响因子：
64.8
作者：
Curry, Andrew
通讯作者：
Curry, Andrew
影响因子：
9.8
作者：
Bersaglieri, T;Sabeti, PC;Hirschhorn, JN
通讯作者：
Hirschhorn, JN
影响因子：
4.8
作者：
Antinozzi, PA;Segall, L;Newgard, CB
通讯作者：
Newgard, CB