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Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans
- Chan, J.L., Matarese, G., Shetty, G.K., Raciti, P., Kelesidis, I., Aufiero, D., De Rosa, V., Perna, F., Fontana, S., Mantzoros, C.S.
- Proceedings of the National Academy of Sciences of the United States of America 2006 v.103 no.22 pp. 8481-8486
- leptin, hormonal regulation, fasting, hormone secretion, luteinizing hormone, metabolism, body weight, immune response, leukocytes, neurosecretory system, T-lymphocytes, body composition, women, mononuclear leukocytes
- To elucidate whether the role of leptin in regulating neuroendocrine and immune function during short-term starvation in healthy humans is permissive, i.e., occurs only when circulating leptin levels are below a critical threshold level, we studied seven normal-weight women during a normoleptinemic-fed state and two states of relative hypoleptinemia induced by 72-h fasting during which we administered either placebo or recombinant methionyl human leptin (r-metHuLeptin) in replacement doses. Fasting for 72 h decreased leptin levels by approximately 80% from a midphysiologic (14.7 ± 2.6 ng/ml) to a low-physiologic (2.8 ± 0.3 ng/ml) level. Administration of r-metHuLeptin during fasting fully restored leptin to physiologic levels (28.8 ± 2.0 ng/ml) and reversed the fasting-associated decrease in overnight luteinizing hormone pulse frequency but had no effect on fasting-induced changes in thyroid-stimulating hormone pulsatility, thyroid and IGF-1 hormone levels, hypothalamic-pituitary-adrenal and renin-aldosterone activity. FSH and sex steroid levels were not altered. Short-term reduction of leptin levels decreased the number of circulating cells of the adaptive immune response, but r-metHuLeptin did not have major effects on their number or in vitro function. Thus, changes of leptin levels within the physiologic range have no major physiologic effects in leptin-replete humans. Studies involving more severe and/or chronic leptin deficiency are needed to precisely define the lower limit of normal leptin levels for each of leptin's physiologic targets.