Fasting, but not exercise, increases adipose triglyceride lipase (ATGL) protein and reduces G(0)/G(1) switch gene 2 (G0S2) protein and mRNA content in human adipose tissue

J Clin Endocrinol Metab. 2011 Aug;96(8):E1293-7. doi: 10.1210/jc.2011-0149. Epub 2011 May 25.

Abstract

Context: Fasting and exercise are characterized by increased lipolysis, but the underlying mechanisms are not fully understood.

Objective: The study was designed to test whether fasting and exercise affect mRNA and protein levels of adipose triglyceride lipase (ATGL) and G(0)/G(1) switch gene 2 (G0S2), a recently discovered ATGL inhibitor, in humans.

Design and participants: We studied eight healthy men (age, 25.5 ± 4.3 yr) for 6 h (a 4-h basal and a 2-h clamp period) on three occasions in a randomized crossover design: 1) in the basal state and after; 2) 72-h fasting; and 3) 1-h exercise (65% VO(2max)). Subcutaneous abdominal adipose tissue (AT) biopsies were taken at t = 30 and 270 min.

Setting: The study was conducted at a university hospital research unit.

Results: Circulating free fatty acids and GH were increased, and C-peptide was decreased by both fasting and exercise. During fasting, insulin failed to suppress free fatty acid levels, suggesting AT insulin resistance. ATGL protein was increased 44% (P < 0.001), and G0S2 mRNA and protein were decreased 56% (P = 0.02) and 54% (P = 0.01), respectively, after fasting, but both ATGL and G0S2 were unaffected by exercise. Protein levels of hormone-sensitive lipase and comparative gene identification-58 were unaffected throughout.

Conclusions: We found increased AT content of ATGL and decreased protein and mRNA content of the ATGL inhibitor G0S2, suggesting increased ATGL activity during fasting, but not after short-term exercise. These findings are compatible with the notion that the ATGL-G0S2 complex is an important long-term regulator of lipolysis under physiological conditions such as fasting in humans.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • C-Peptide / blood
  • Calorimetry, Indirect
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cross-Over Studies
  • Exercise / physiology*
  • Fasting / physiology*
  • Fatty Acids, Nonesterified / blood
  • Glucose Clamp Technique
  • Human Growth Hormone / blood
  • Humans
  • Insulin / blood
  • Lipase / genetics*
  • Lipase / metabolism
  • Lipolysis / physiology
  • Male
  • RNA, Messenger / metabolism
  • Subcutaneous Fat / physiology*
  • Young Adult

Substances

  • C-Peptide
  • Cell Cycle Proteins
  • Fatty Acids, Nonesterified
  • G0S2 protein, human
  • Insulin
  • RNA, Messenger
  • Human Growth Hormone
  • Lipase
  • PNPLA2 protein, human