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Cell Metab DOI:10.1016/j.cmet.2015.03.006

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

Publication TypeJournal Article
Year of Publication2015
AuthorsDai, N, Zhao, L, Wrighting, D, Krämer, D, Majithia, A, Wang, Y, Cracan, V, Borges-Rivera, D, Mootha, VK, Nahrendorf, M, Thorburn, DR, Minichiello, L, Altshuler, D, Avruch, J
JournalCell Metab
Date Published2015 Apr 07
KeywordsAdipose Tissue, Brown, Analysis of Variance, Animals, Base Sequence, Body Temperature Regulation, Energy Metabolism, Gene Expression Regulation, Insulin Resistance, Ion Channels, Mice, Mice, Knockout, Mitochondrial Proteins, Molecular Sequence Data, Obesity, RNA-Binding Proteins, Sequence Analysis, RNA, Uncoupling Protein 1

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.


Alternate JournalCell Metab.
PubMed ID25863250
PubMed Central IDPMC4663978
Grant ListP30 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