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Link to original content: https://pubmed.ncbi.nlm.nih.gov/16714386/
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Controlled Clinical Trial
. 2006 May 30;103(22):8481-6.
doi: 10.1073/pnas.0505429103. Epub 2006 May 19.

Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans

Affiliations
Controlled Clinical Trial

Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans

Jean L Chan et al. Proc Natl Acad Sci U S A. .

Abstract

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.

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Conflict of interest statement

Conflict of interest statement: No conflicts declared.

Figures

Fig. 1.
Fig. 1.
Twenty-four-hour profile (8 a.m.–8 p.m.) of average (n = 7) leptin (a) and representative LH (b) levels on day 3 of a baseline fed state (Top), 72-h fasting with placebo (Middle), or 72-h fasting with replacement-dose r-metHuLeptin (Bottom).
Fig. 2.
Fig. 2.
Leptin depletion or neutralization inhibits polyclonal T cell proliferation and mixed lymphocyte reactions (MLR), respectively. (ac)The proliferative response of T lymphocytes to polyclonal stimuli (OKT3, PHA, and PMA/Iono) from controls is completely inhibited in medium with human serum depleted of leptin. Addition of recombinant human leptin (at 100 ng/ml final concentration) completely reverses this phenomenon. (d) Anti-leptin blocking Abs partially inhibit the antigen-specific proliferative response of T cells during MLR. HS, human serum.

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