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

Abstract

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% VO2max). 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.