IGF2BP2/IMP2-Deficient Mice Resist Obesity Through Enhanced Translation of Ucp1 MRNA and Other MRNAs Encoding Mitochondrial Proteins

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2015 Apr 12

PMID 25863250

Citations 104

Authors

Ning Dai

Liping Zhao

Diedra Wrighting

Dana Kramer

Amit Majithia

Yanqun Wang

Valentin Cracan

Diego Borges-Rivera

Vamsi K Mootha

Matthias Nahrendorf

David R Thorburn

Liliana Minichiello

David Altshuler

Joseph Avruch

Affiliations

Soon will be listed here.

Abstract

Although variants in the IGF2BP2/IMP2 gene confer risk for type 2 diabetes, IMP2, an RNA binding protein, is not known to regulate metabolism. Imp2(-/-) mice gain less lean mass after weaning and have increased lifespan. Imp2(-/-) mice are highly resistant to diet-induced obesity and fatty liver and display superior glucose tolerance and insulin sensitivity, increased energy expenditure, and better defense of core temperature on cold exposure. Imp2(-/-) brown fat and Imp2(-/-) brown adipocytes differentiated in vitro contain more UCP1 polypeptide than Imp2(+/+) despite similar levels of Ucp1 mRNA; the Imp2(-/-)adipocytes also exhibit greater uncoupled oxygen consumption. IMP2 binds the mRNAs encoding Ucp1 and other mitochondrial components, and most exhibit increased translational efficiency in the absence of IMP2. In vitro IMP2 inhibits translation of mRNAs bearing the Ucp1 untranslated segments. Thus IMP2 limits longevity and regulates nutrient and energy metabolism in the mouse by controlling the translation of its client mRNAs.

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