IGF2BP2/IMP2-Deficient mice resist obesity through enhanced translation of Ucp1 mRNA and Other mRNAs encoding mitochondrial proteins.

Cell Metab
Authors
Keywords
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.

Year of Publication
2015
Journal
Cell Metab
Volume
21
Issue
4
Pages
609-21
Date Published
2015 Apr 07
ISSN
1932-7420
URL
DOI
10.1016/j.cmet.2015.03.006
PubMed ID
25863250
PubMed Central ID
PMC4663978
Links
Grant list
P30 DK040561 / DK / NIDDK NIH HHS / United States
T32 GM007287 / GM / NIGMS NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
P30DK057521 / DK / NIDDK NIH HHS / United States
P30 DK057521 / DK / NIDDK NIH HHS / United States
R37DK17776 / DK / NIDDK NIH HHS / United States
R37 DK017776 / DK / NIDDK NIH HHS / United States