| Literature DB >> 33058756 |
Lifeng Wang1, Nasa Sinnott-Armstrong2, Alexandre Wagschal1, Abigail R Wark3, Joao-Paulo Camporez4, Rachel J Perry4, Fei Ji5, Yoojin Sohn1, Justin Oh1, Su Wu1, Jessica Chery1, Bahareh Nemati Moud6, Alham Saadat7, Simon N Dankel8, Gunnar Mellgren8, Divya Sri Priyanka Tallapragada8, Sophie Madlen Strobel9, Mi-Jeong Lee10, Ryan Tewhey11, Pardis C Sabeti12, Anne Schaefer13, Andreas Petri14, Sakari Kauppinen14, Raymond T Chung15, Alexander Soukas16, Joseph Avruch17, Susan K Fried10, Hans Hauner18, Ruslan I Sadreyev5, Gerald I Shulman4, Melina Claussnitzer19, Anders M Näär20.
Abstract
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.Entities:
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Year: 2020 PMID： 33058756 PMCID： PMC8092355 DOI： 10.1016/j.cell.2020.09.017
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582