Impact of fasting on growth hormone signaling and action in muscle and fat

Louise Moller; Lisa Dalman; Helene Norrelund; Nils Billestrup; Jan Frystyk; Niels Moller; Jens Otto Lunde Jorgensen

doi:10.1210/jc.2008-1385

Impact of fasting on growth hormone signaling and action in muscle and fat

Louise Moller, Lisa Dalman, Helene Norrelund, Nils Billestrup, Jan Frystyk, Niels Moller, Jens Otto Lunde Jorgensen

Inflammation, Metabolism and Oxidation

29 Citations (Scopus)

Abstract

CONTEXT: 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. DESIGN: We conducted a randomized crossover study. SUBJECTS: Ten healthy men (age 24.3 +/- 0.6 yr, body mass index 23.1 +/- 0.4 kg/m(2)) participated. INTERVENTION: 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. MAIN OUTCOME MEASURES: 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). CONCLUSION: 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.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	94
Issue number	3
Pages (from-to)	965-72
Number of pages	7
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2008-1385
Publication status	Published - 2008

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10.1210/jc.2008-1385

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@article{4f3c92d0333411df8ed1000ea68e967b,

title = "Impact of fasting on growth hormone signaling and action in muscle and fat",

abstract = "CONTEXT: 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. DESIGN: We conducted a randomized crossover study. SUBJECTS: Ten healthy men (age 24.3 +/- 0.6 yr, body mass index 23.1 +/- 0.4 kg/m(2)) participated. INTERVENTION: 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. MAIN OUTCOME MEASURES: 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). CONCLUSION: 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.",

author = "Louise Moller and Lisa Dalman and Helene Norrelund and Nils Billestrup and Jan Frystyk and Niels Moller and Jorgensen, {Jens Otto Lunde}",

note = "Keywords: Adult; C-Peptide; Cross-Over Studies; Fasting; Glucose; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Janus Kinase 2; Lipid Metabolism; Lipolysis; Male; Metabolic Clearance Rate; Muscle, Skeletal; STAT5 Transcription Factor; Signal Transduction",

year = "2008",

doi = "10.1210/jc.2008-1385",

language = "English",

volume = "94",

pages = "965--72",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "3",

}

TY - JOUR

T1 - Impact of fasting on growth hormone signaling and action in muscle and fat

AU - Moller, Louise

AU - Dalman, Lisa

AU - Norrelund, Helene

AU - Billestrup, Nils

AU - Frystyk, Jan

AU - Moller, Niels

AU - Jorgensen, Jens Otto Lunde

N1 - Keywords: Adult; C-Peptide; Cross-Over Studies; Fasting; Glucose; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Janus Kinase 2; Lipid Metabolism; Lipolysis; Male; Metabolic Clearance Rate; Muscle, Skeletal; STAT5 Transcription Factor; Signal Transduction

PY - 2008

Y1 - 2008

N2 - CONTEXT: 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. DESIGN: We conducted a randomized crossover study. SUBJECTS: Ten healthy men (age 24.3 +/- 0.6 yr, body mass index 23.1 +/- 0.4 kg/m(2)) participated. INTERVENTION: 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. MAIN OUTCOME MEASURES: 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). CONCLUSION: 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.

AB - CONTEXT: 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. DESIGN: We conducted a randomized crossover study. SUBJECTS: Ten healthy men (age 24.3 +/- 0.6 yr, body mass index 23.1 +/- 0.4 kg/m(2)) participated. INTERVENTION: 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. MAIN OUTCOME MEASURES: 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). CONCLUSION: 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.

U2 - 10.1210/jc.2008-1385

DO - 10.1210/jc.2008-1385

M3 - Journal article

C2 - 19066303

SN - 0021-972X

VL - 94

SP - 965

EP - 972

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 3

ER -

Impact of fasting on growth hormone signaling and action in muscle and fat

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