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. DESIGN: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.
RCT Entities:
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. DESIGN: 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.
Authors: Christos S Mantzoros; Faidon Magkos; Mary Brinkoetter; Elizabeth Sienkiewicz; Tina A Dardeno; Sang-Yong Kim; Ole-Petter R Hamnvik; Anastasia Koniaris Journal: Am J Physiol Endocrinol Metab Date: 2011-07-26 Impact factor: 4.310
Authors: Harry R Kissileff; John C Thornton; Migdalia I Torres; Katherine Pavlovich; Laurel S Mayer; Vamsi Kalari; Rudolph L Leibel; Michael Rosenbaum Journal: Am J Clin Nutr Date: 2012-01-11 Impact factor: 7.045
Authors: Janette H Quennell; Alicia C Mulligan; Alexander Tups; Xinhuai Liu; Sarah J Phipps; Christopher J Kemp; Allan E Herbison; David R Grattan; Greg M Anderson Journal: Endocrinology Date: 2009-01-29 Impact factor: 4.736
Authors: Louis J Aronne; Kevin D Hall; John M Jakicic; Rudolph L Leibel; Michael R Lowe; Michael Rosenbaum; Samuel Klein Journal: Obesity (Silver Spring) Date: 2021-04 Impact factor: 9.298