The effect of pegylated human recombinant leptin (PEG-OB) on neuroendocrine adaptations to semi-starvation in overweight men.
OBJECTIVE
Starvation induces a complex neuroendocrine response in humans thought to have evolved to defend against reduced energy intake. The drop in leptin levels observed during fasting has been implicated as a factor that triggers this adaptive response. To explore this hypothesis, we executed a randomized, double-blind, placebo-controlled study to investigate whether elevated leptin levels using long-acting pegylated human recombinant leptin (PEG-OB) influenced the neuroendocrine responses to semi-starvation in human subjects.


METHODS
Twenty-four overweight male subjects (mean+/-s.e.m.; 34.8+/-1.3 yrs; 28.8+/-0.5 kg/m(2)) were prescribed a very low energy diet (2.1 MJ/day) to induce a state of semi-starvation for the next 46 days. In addition, all subjects received a weekly treatment of 80 mg PEG-OB or matching placebo. Hormone measurements were performed throughout the study period and included 5-h frequent hormone samplings and 24-h urine collections.


RESULTS
Weekly subcutaneous administration of PEG-OB led to significant additional weight loss (2.8 kg) but it did not reverse the fasting-induced changes in the thyroid, corticotropic, somatotropic axes and sympathetic nervous system activity. However, after adjustment for weight loss, the drop in mean luteinizing hormone levels was attenuated in the PEG-OB group compared with the placebo group.


CONCLUSIONS
These results suggest that a reduced level of leptin accompanying food restriction might be a component of the fasting-induced neuroendocrine inhibition of the human reproductive axis.
Hukshorn
Chris J
CJ
Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Human Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. c.hukshorn@hb.unimaas.nl
Menheere
Paul P C A
PP
Westerterp-Plantenga
Margriet S
MS
Saris
Wim H M
WH
D000222:Adaptation, Physiological; D000293:Adolescent; D000328:Adult; D002149:Energy Intake; D004734:Energy Metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D020738:Leptin / Q000008:administration & dosage* / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000178:diet therapy / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D013217:Starvation / Q000097:blood*; D015431:Weight Loss / Q000187:drug effects
D006728:Hormones; D020738:Leptin; D011994:Recombinant Proteins; D011092:Polyethylene Glycols