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MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis.

Published version
Peer-reviewed

Type

Article

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Authors

Godbersen, Svenja 
Farooqi, I Sadaf 

Abstract

MicroRNAs (miRNAs) modulate physiological responses by repressing the expression of gene networks. We found that global deletion of microRNA-7 (miR-7), the most enriched miRNA in the hypothalamus, causes obesity in mice. Targeted deletion of miR-7 in Single-minded homolog 1 (Sim1) neurons, a critical component of the hypothalamic melanocortin pathway, causes hyperphagia, obesity and increased linear growth, mirroring Sim1 and Melanocortin-4 receptor (MC4R) haplo-insufficiency in mice and humans. We identified Snca (α-Synuclein) and Igsf8 (Immunoglobulin Superfamily Member 8) as miR-7 target genes that act in Sim1 neurons to regulate body weight and endocrine axes. In humans, MIR-7-1 is located in the last intron of HNRNPK, whose promoter drives the expression of both genes. Genetic variants at the HNRNPK locus that reduce its expression are associated with increased height and truncal fat mass. These findings demonstrate that miR-7 suppresses gene networks involved in the hypothalamic melanocortin pathway to regulate mammalian energy homeostasis.

Description

Funder: National Institute for Health Research (NIHR)


Funder: Fondation Botnar

Keywords

Animals, Homeostasis, Humans, Immunoglobulins, Mammals, Melanocortins, Mice, MicroRNAs, Obesity, Receptor, Melanocortin, Type 4, Transcription Factors, alpha-Synuclein

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (207462/Z/17/Z)