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Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency States

Division of Endocrinology, Diabetes, and Metabolism (J.L.C., C.J.W., P.R., J.B., T.K., I.K., C.S.M.), Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; and Division of Endocrinology and Metabolism (M.L.J., M.O.T.), University of Virginia Health System, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Christos S. Mantzoros, M.D., D.Sc., Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, ST 816, Boston, Massachusetts 02215. E-mail: cmantzor{at}bidmc.harvard.edu.

Context: States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels.

Objective: The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit.

Design, Setting, Patients, and Intervention: We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2–3 months of r-metHuLeptin treatment.

Main Outcome Measures: GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured.

Results: During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month.

Conclusions: The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

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				A. M Brennan, J. H Lee, S. Tsiodras, J. L Chan, J. Doweiko, S. N Chimienti, S. G Wadhwa, A. W Karchmer, and C. S Mantzoros r-metHuLeptin improves highly active antiretroviral therapy-induced lipoatrophy and the metabolic syndrome, but not through altering circulating IGF and IGF-binding protein levels: observational and interventional studies in humans Eur. J. Endocrinol., February 1, 2009; 160(2): 173 - 176. [Abstract] [Full Text] [PDF]