Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice.

Autor:	Tsai SY; Buck Institute for Research on Aging, Novato, CA 94945, USA., Rodriguez AA; Buck Institute for Research on Aging, Novato, CA 94945, USA., Dastidar SG; Division of Biological Sciences, Departments of Pediatrics, Cellular and Molecular Medicine, and Neurosciences, Institute for Genomic Medicine, and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92903, USA., Del Greco E; Buck Institute for Research on Aging, Novato, CA 94945, USA., Carr KL; Buck Institute for Research on Aging, Novato, CA 94945, USA., Sitzmann JM; Buck Institute for Research on Aging, Novato, CA 94945, USA., Academia EC; Buck Institute for Research on Aging, Novato, CA 94945, USA., Viray CM; Buck Institute for Research on Aging, Novato, CA 94945, USA., Martinez LL; Buck Institute for Research on Aging, Novato, CA 94945, USA., Kaplowitz BS; Buck Institute for Research on Aging, Novato, CA 94945, USA., Ashe TD; Division of Biological Sciences, Departments of Pediatrics, Cellular and Molecular Medicine, and Neurosciences, Institute for Genomic Medicine, and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92903, USA., La Spada AR; Division of Biological Sciences, Departments of Pediatrics, Cellular and Molecular Medicine, and Neurosciences, Institute for Genomic Medicine, and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92903, USA; Rady Children's Hospital, San Diego, CA 92123, USA. Electronic address: alaspada@ucsd.edu., Kennedy BK; Buck Institute for Research on Aging, Novato, CA 94945, USA. Electronic address: bkennedy@buckinstitute.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2016 Aug 16; Vol. 16 (7), pp. 1903-14. Date of Electronic Publication: 2016 Aug 04.
DOI:	10.1016/j.celrep.2016.07.029
Abstrakt:	Obesity is a major risk factor driving the global type II diabetes pandemic. However, the molecular factors linking obesity to disease remain to be elucidated. Gender differences are apparent in humans and are also observed in murine models. Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), which, upon HFD feeding, becomes significantly reduced in the skeletal muscle and adipose tissue of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1 transgenic mice also exhibit reduced white adipose tissue accumulation accompanied by decreased circulating levels of leptin and triglycerides. Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced obesity and metabolic decline on a normal diet. These results demonstrate that 4E-BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity and energy metabolism. (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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