Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans.
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.
Chan
Jean L
JL
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Matarese
Giuseppe
G
Shetty
Greeshma K
GK
Raciti
Patricia
P
Kelesidis
Iosif
I
Aufiero
Daniela
D
De Rosa
Veronica
V
Perna
Francesco
F
Fontana
Silvia
S
Mantzoros
Christos S
CS
D000222:Adaptation, Physiological / Q000187:drug effects / Q000276:immunology; D000273:Adipose Tissue; D000328:Adult; D050218:Body Fat Distribution; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D005215:Fasting; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D007958:Leukocyte Count; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D006728:Hormones; D020738:Leptin; D007334:Insulin-Like Growth Factor I