A MicroRNA Linking Human Positive Selection and Metabolic Disorders

Lifeng Wang; Nasa Sinnott-Armstrong; Alexandre Wagschal; Abigail R. Wark; Joao Paulo Camporez; Rachel J. Perry; Fei Ji; Yoojin Sohn; Justin Oh; Su Wu; Jessica Chery; Bahareh Nemati Moud; Alham Saadat; Simon N. Dankel; Gunnar Mellgren; Divya Sri Priyanka Tallapragada; Sophie Madlen Strobel; Mi Jeong Lee; Ryan Tewhey; Pardis C. Sabeti; Anne Schaefer; Andreas Petri; Sakari Kauppinen; Raymond T. Chung; Alexander Soukas; Joseph Avruch; Susan K. Fried; Hans Hauner; Ruslan I. Sadreyev; Gerald I. Shulman; Melina Claussnitzer; Anders M. Näär

doi:10.1016/j.cell.2020.09.017

A MicroRNA Linking Human Positive Selection and Metabolic Disorders

Lifeng Wang, Nasa Sinnott-Armstrong, Alexandre Wagschal, Abigail R. Wark, Joao Paulo Camporez, Rachel J. Perry, Fei Ji, Yoojin Sohn, Justin Oh, Su Wu, Jessica Chery, Bahareh Nemati Moud, Alham Saadat, Simon N. Dankel, Gunnar Mellgren, Divya Sri Priyanka Tallapragada, Sophie Madlen Strobel, Mi Jeong Lee, Ryan Tewhey, Pardis C. SabetiAnne Schaefer, Andreas Petri, Sakari Kauppinen, Raymond T. Chung, Alexander Soukas, Joseph Avruch, Susan K. Fried, Hans Hauner, Ruslan I. Sadreyev, Gerald I. Shulman, Melina Claussnitzer, Anders M. Näär^*

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

38 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Cell
Vol/bind	183
Udgave nummer	3
Sider (fra-til)	684-701.e14
ISSN	0092-8674
DOI	https://doi.org/10.1016/j.cell.2020.09.017
Status	Udgivet - 29 okt. 2020

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10.1016/j.cell.2020.09.017

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Wang, L., Sinnott-Armstrong, N., Wagschal, A., Wark, A. R., Camporez, J. P., Perry, R. J., Ji, F., Sohn, Y., Oh, J., Wu, S., Chery, J., Moud, B. N., Saadat, A., Dankel, S. N., Mellgren, G., Tallapragada, D. S. P., Strobel, S. M., Lee, M. J., Tewhey, R., ... Näär, A. M. (2020). A MicroRNA Linking Human Positive Selection and Metabolic Disorders. Cell, 183(3), 684-701.e14. https://doi.org/10.1016/j.cell.2020.09.017

@article{b2ffa10994d54da086aaff51fc8b7fd1,

title = "A MicroRNA Linking Human Positive Selection and Metabolic Disorders",

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.",

author = "Lifeng Wang and Nasa Sinnott-Armstrong and Alexandre Wagschal and Wark, {Abigail R.} and Camporez, {Joao Paulo} and Perry, {Rachel J.} and Fei Ji and Yoojin Sohn and Justin Oh and Su Wu and Jessica Chery and Moud, {Bahareh Nemati} and Alham Saadat and Dankel, {Simon N.} and Gunnar Mellgren and Tallapragada, {Divya Sri Priyanka} and Strobel, {Sophie Madlen} and Lee, {Mi Jeong} and Ryan Tewhey and Sabeti, {Pardis C.} and Anne Schaefer and Andreas Petri and Sakari Kauppinen and Chung, {Raymond T.} and Alexander Soukas and Joseph Avruch and Fried, {Susan K.} and Hans Hauner and Sadreyev, {Ruslan I.} and Shulman, {Gerald I.} and Melina Claussnitzer and N{\"a}{\"a}r, {Anders M.}",

year = "2020",

month = oct,

day = "29",

doi = "10.1016/j.cell.2020.09.017",

language = "English",

volume = "183",

pages = "684--701.e14",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "3",

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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 2020, 'A MicroRNA Linking Human Positive Selection and Metabolic Disorders', Cell, bind 183, nr. 3, s. 684-701.e14. https://doi.org/10.1016/j.cell.2020.09.017

TY - JOUR

T1 - A MicroRNA Linking Human Positive Selection and Metabolic Disorders

AU - Wang, Lifeng

AU - Sinnott-Armstrong, Nasa

AU - Wagschal, Alexandre

AU - Wark, Abigail R.

AU - Camporez, Joao Paulo

AU - Perry, Rachel J.

AU - Ji, Fei

AU - Sohn, Yoojin

AU - Oh, Justin

AU - Wu, Su

AU - Chery, Jessica

AU - Moud, Bahareh Nemati

AU - Saadat, Alham

AU - Dankel, Simon N.

AU - Mellgren, Gunnar

AU - Tallapragada, Divya Sri Priyanka

AU - Strobel, Sophie Madlen

AU - Lee, Mi Jeong

AU - Tewhey, Ryan

AU - Sabeti, Pardis C.

AU - Schaefer, Anne

AU - Petri, Andreas

AU - Kauppinen, Sakari

AU - Chung, Raymond T.

AU - Soukas, Alexander

AU - Avruch, Joseph

AU - Fried, Susan K.

AU - Hauner, Hans

AU - Sadreyev, Ruslan I.

AU - Shulman, Gerald I.

AU - Claussnitzer, Melina

AU - Näär, Anders M.

PY - 2020/10/29

Y1 - 2020/10/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85094173709&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2020.09.017

DO - 10.1016/j.cell.2020.09.017

M3 - Journal article

C2 - 33058756

AN - SCOPUS:85094173709

SN - 0092-8674

VL - 183

SP - 684-701.e14

JO - Cell

JF - Cell

IS - 3

ER -

A MicroRNA Linking Human Positive Selection and Metabolic Disorders

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