Background: Growth hormone (GH) potently stimulates lipolysis, and after GH exposure, levels of serum free fatty acids (FFAs) increase in a distinct temporal pattern characterized by a 1-hour lag phase and a peak after 3 hours followed by a gradual return to baseline. This effect predominantly operates during fasting and promotes utilization of lipids from adipose tissue (AT) at the expense of glucose and protein. Prolonged fasting also downregulates the expression of the G0/G1 switch gene 2 (G0S2), which is a suppressor of the adipose triglyceride lipase (ATGL). The molecular mechanisms underlying the lipolytic effect of GH, including putative effects on G0S2, remain elusive.
Aim: To study expression of the lipolytic regulators in consecutive human AT biopsies after a GH bolus.
Methods: In a randomized, placebo-controlled, cross-over study nine healthy, obese men were examined on two occasions: 1) after an IV GH bolus [GH], and 2) after injection of a GH receptor antagonist [control]. Serum FFAs were measured. Biopsies from subcutaneous AT were obtained at t=0, t=60, t=180, and t=300 min, and gene and protein expression of putative lipolytic regulators were studied by RT-qPCR and western blotting.
Results: Serum FFAs increased 1 hour after GH exposure and peaked after 3 hours. In AT, we recorded phosphorylation of signal transducer and activator of transcription 5 (STAT5) after 1 hour and increased genexpression of cytokine-inducible SH2-containing protein (CISH) and insulin-like growth factor-1 (IGF-1) after 3 hours, indicative of GH signaling. Furthermore, GH exposure suppressed gene expression of the ATGL inhibitory protein G0S2 in addition to upregulation of PTEN, a known suppressor of insulin-stimulated anti-lipolysis.
Conclusions: 1) An intravenous GH bolus acutely induces GH receptor signaling in human AT in vivo. 2) This was associated with a significant increase in serum FFA levels after 1-3 hours and the underlying mechanisms involves suppression of anti-lipolytic signaling in AT. 3) Characterization of the targets for GH-induced lipolysis may have physiological and therapeutic implications.
18 - 21 May 2019
European Society of Endocrinology