Impact of fasting on growth hormone signaling and action in muscle and fat.
BACKGROUND
Whether GH promotes IGF-I production or lipolysis depends on nutritional status, but the underlying mechanisms remain unknown.


OBJECTIVE
To investigate the impact of fasting on GH-mediated changes in substrate metabolism, insulin sensitivity, and signaling pathways.


METHODS
We conducted a randomized crossover study.


METHODS
Ten healthy men (age 24.3 +/- 0.6 yr, body mass index 23.1 +/- 0.4 kg/m(2)) participated.


METHODS
A GH bolus administered 1) postabsorptively and 2) in the fasting state (37.5 h). Skeletal muscle and adipose tissue biopsies were taken, and a hyperinsulinemic-euglycemic clamp was performed on both occasions.


METHODS
Metabolic clearance rate (MCR) of GH, substrate metabolism, and insulin sensitivity were measured. Biopsies were subjected to Western blotting for expression of signaling proteins and to RT-PCR for expression of suppressor of cytokine signaling protein 3 and IGF-I mRNA.


RESULTS
Fasting was associated with reduced MCR of GH (P < 0.01), enhanced lipolytic responsiveness to GH, decreased insulin sensitivity (P < 0.01), and reduced IGF-I bioactivity (P = 0.04). After the GH bolus, phosphorylation of signal transducers and activators of transcription protein 5b (pSTAT5b) were observed in both conditions; however, the phospho-STAT5b/STAT5b ratio was significantly decreased in the fasting state (muscle P = 0.02 and fat P = 0.02).


CONCLUSIONS
The combination of fasting and GH exposure translates into enhanced lipolysis, reduced IGF-I activity and insulin sensitivity, and blunted activation of the Janus kinase (JAK)/STAT pathway. Whether this change in signaling activity is related to the change in MCR of GH and/or the concomitant shift in the metabolic effects of GH merits future attention.
Moller
Louise
L
Medical Department M, Aarhus Sygehus, Norrebrogade 44, DK-8000 Aarhus, Denmark. louisem@dadlnet.dk
Dalman
Lisa
L
Norrelund
Helene
H
Billestrup
Nils
N
Frystyk
Jan
J
Moller
Niels
N
Jorgensen
Jens Otto Lunde
JO
D000328:Adult; D002096:C-Peptide / Q000032:analysis; D018592:Cross-Over Studies; D005215:Fasting / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D019382:Human Growth Hormone / Q000493:pharmacokinetics / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D053614:Janus Kinase 2 / Q000378:metabolism; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D008657:Metabolic Clearance Rate; D018482:Muscle, Skeletal / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D002096:C-Peptide; C032231:IGFBP1 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D005947:Glucose