1. Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice.
- Author
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Tsai SY, Rodriguez AA, Dastidar SG, Del Greco E, Carr KL, Sitzmann JM, Academia EC, Viray CM, Martinez LL, Kaplowitz BS, Ashe TD, La Spada AR, and Kennedy BK
- Subjects
- Adaptor Proteins, Signal Transducing, Adipose Tissue, White pathology, Aging pathology, Animals, Carrier Proteins metabolism, Cell Cycle Proteins, Diet, High-Fat adverse effects, Eukaryotic Initiation Factors, Female, Gene Expression Regulation, Humans, Leptin blood, Leptin genetics, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Obesity etiology, Obesity metabolism, Obesity pathology, Phosphoproteins metabolism, Sex Factors, Signal Transduction, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases metabolism, Transgenes, Triglycerides blood, Adipose Tissue, White metabolism, Aging genetics, Carrier Proteins genetics, Insulin Resistance genetics, Obesity genetics, Phosphoproteins genetics
- Abstract
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.)
- Published
- 2016
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