Endocrine Abstracts

Context: Obesity is accompanied by blunted GH secretion but relatively normal serum IGF-I levels, which suggests increased GH sensitivity. This, however, remains to be tested at the level of GH signaling in human subjects.

Objective: To compare the effects of an acute intravenous GH bolus in obese vs normal weight subjects on GH signaling pathways in adipose and muscle tissue, substrate metabolism and insulin sensitivity.

Subjects and methods: Nine obese (BMI 35.7±0.9) and nine lean (BMI 21.5±0.4) young men were studied twice in a randomized crossover design: (1) After an overnight fast (12 h) (‘Control’) and (2) After an overnight fast with an intravenous GH bolus (0.005 mg/kg) (‘GH bolus’). Each study day consisted of a 4-h basal period (t=0 – t=240 min) followed by a 2-h hyperinsulinemic, euglycemic clamp (HEC). GH was injected at t=0 and biopsies from muscle and fat were drawn. Muscle and fat biopsies were taken at t=60 min.

Results: Spontaneous serum GH levels were lower in obese subjects, whereas the PK of the GH bolus was comparable. The GH bolus was associated with a BMI-independent increase in STAT5b phosphorylation and CISH mRNA transcription in muscle and adipose tissue. The GH bolus, however, produced a larger relative increase in serum IGF-I levels in obese subjects (P < 0.01). GH acutely stimulated lipolysis (ΔFFA in serum, serum palmitate levels and fluxes) to the same extent in both groups. GH significantly reduced glucose uptake during the HEC in both groups (P=0.23), but GH only antagonized insulin-induced suppression of endogenous glucose production (EGP) in the obese (P=0.01).

Conclusions: (1) Acute GH exposure induces pSTAT5b and CISH mRNA and transcription in fat and muscle, and lipolysis to the same extent in obese and lean subjects, (2) A GH-induced relative increase in serum IGF-I levels and suppression of EGP was only recorded in the obese, (3) Our data thus suggest increased hepatic sensitivity to GH in obesity, which in turn may contribute to the blunted endogenous GH secretion.