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

Cell Rep. 2016 Aug 16;16(7):1903-14. doi: 10.1016/j.celrep.2016.07.029. Epub 2016 Aug 4.

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adipose Tissue, White / metabolism*
  • Adipose Tissue, White / pathology
  • Aging / genetics*
  • Aging / pathology
  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins
  • Diet, High-Fat / adverse effects
  • Eukaryotic Initiation Factors
  • Female
  • Gene Expression Regulation
  • Humans
  • Insulin Resistance / genetics*
  • Leptin / blood
  • Leptin / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Obesity / etiology
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Sex Factors
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Transgenes
  • Triglycerides / blood

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • Eif4ebp1 protein, mouse
  • Eukaryotic Initiation Factors
  • Leptin
  • Phosphoproteins
  • Triglycerides
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases