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Activating Autophagy by Aerobic Exercise in Mice
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Exercise increases TBC1D1 phosphorylation in human skeletal muscle.

Niels Jessen1, Ding An, Aina S Lihn

  • 1Joslin Diabetes Center, Boston, MA 02215, USA.

American Journal of Physiology. Endocrinology and Metabolism
|April 21, 2011
PubMed
Summary

Exercise and diet improve insulin sensitivity by increasing glucose uptake in muscle. A study found exercise, but not diet-induced weight loss, alters AS160 and TBC1D1 protein phosphorylation in human skeletal muscle.

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Area of Science:

  • Exercise physiology
  • Molecular biology
  • Metabolic disease research

Background:

  • Exercise and weight loss enhance insulin sensitivity and glucose uptake in skeletal muscle, crucial for type 2 diabetes management.
  • Rodent studies link Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1 phosphorylation to muscle glucose uptake.
  • Regulation of AS160 and TBC1D1 in human skeletal muscle remains less understood compared to rodent models.

Purpose of the Study:

  • To investigate the effects of dietary intervention and acute exercise on site-specific phosphorylation of AS160 and TBC1D1 in human skeletal muscle.
  • To examine changes in AMPK activity and Akt phosphorylation in response to these interventions.
  • To elucidate the molecular mechanisms of glucose regulation in human muscle.

Main Methods:

  • Ten obese subjects underwent a 2-week dietary intervention followed by muscle biopsies.
  • Biopsies were collected at rest and post-exercise (30 min at 70% VO2 max).
  • Muscle lysates were analyzed for AMPK activity, Akt phosphorylation, and specific phosphorylation sites on AS160 and TBC1D1.

Main Results:

  • Diet-induced weight loss (4.2 kg) improved insulin sensitivity but did not alter signaling protein expression or phosphorylation.
  • Exercise increased muscle AMPKα2 activity but not Akt phosphorylation.
  • Exercise enhanced phosphorylation at AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660), indicating regulation of these proteins.

Conclusions:

  • Acute exercise effectively modulates TBC1D1 and AS160 phosphorylation at multiple sites in human skeletal muscle.
  • Diet-induced weight loss, despite improving insulin sensitivity, did not impact these specific signaling pathways.
  • These findings highlight the distinct molecular effects of exercise versus diet on glucose regulation mechanisms in human muscle.