title: Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice.
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.
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors: Shih-Yin
authors: SY
authors: Tsai
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors: Ariana A
authors: AA
authors: Rodriguez
authors: 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.
authors: Somasish G
authors: SG
authors: Dastidar
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors: Elizabeth
authors: E
authors: Del Greco
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors: Kaili Lia
authors: KL
authors: Carr
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors: Joanna M
authors: JM
authors: Sitzmann
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors: Emmeline C
authors: EC
authors: Academia
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors: Christian Michael
authors: CM
authors: Viray
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors: Lizbeth Leon
authors: LL
authors: Martinez
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors: Brian Stephen
authors: BS
authors: Kaplowitz
authors: 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.
authors: Travis D
authors: TD
authors: Ashe
authors: 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.
authors: Albert R
authors: AR
authors: La Spada
authors: Buck Institute for Research on Aging, Novato, CA 94945, USA. Electronic address: bkennedy@buckinstitute.org.
authors: Brian K
authors: BK
authors: Kennedy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D059305:Diet, High-Fat / Q000009:adverse effects; D039642:Eukaryotic Initiation Factors; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D020738:Leptin / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D019076:Transgenes; D014280:Triglycerides / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D020738:Leptin; D010750:Phosphoproteins; D014280:Triglycerides; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases