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A MicroRNA Linking Human Positive Selection and Metabolic Disorders.
- Source :
-
Cell [Cell] 2020 Oct 29; Vol. 183 (3), pp. 684-701.e14. Date of Electronic Publication: 2020 Oct 14. - Publication Year :
- 2020
-
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.<br />Competing Interests: Declaration of Interests A.M.N. has issued patents on miR-128-1 (U.S. Pat. Nos. 9,045,749; 9,476,046; 9,789,132).<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Adipocytes, Brown pathology
Adiposity
Alleles
Animals
Cell Differentiation
Cell Line
Cells, Cultured
Diet, High-Fat
Energy Metabolism
Epigenesis, Genetic
Genetic Loci
Glucose metabolism
Homeostasis
Humans
Hypertrophy
Insulin Resistance
Leptin deficiency
Leptin metabolism
Male
Mammals genetics
Mice, Inbred C57BL
Mice, Obese
MicroRNAs metabolism
Obesity genetics
Oligonucleotides metabolism
Species Specificity
Metabolic Diseases genetics
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 183
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 33058756
- Full Text :
- https://doi.org/10.1016/j.cell.2020.09.017