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

Jean L. Chan, Giuseppe Matarese, Greeshma K. Shetty, Patricia Raciti, Iosif Kelesidis, Daniela Aufiero, Veronica De Rosa, Francesco Perna, Silvia Fontana, Christos S. Mantzoros

Research output: Contribution to journalArticle

128 Citations (Scopus)

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 ≈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.

Original languageEnglish
Pages (from-to)8481-8486
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number22
DOIs
Publication statusPublished - May 30 2006

Fingerprint

Fasting
recombinant methionyl human leptin
Hypothalamic Hormones
Adaptive Immunity
Thyrotropin
Luteinizing Hormone
Starvation
Leptin
Aldosterone
Insulin-Like Growth Factor I
Renin
Thyroid Gland
Cell Count
Steroids
Placebos
Weights and Measures

Keywords

  • Fasting
  • Reproductive

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans. / Chan, Jean L.; Matarese, Giuseppe; Shetty, Greeshma K.; Raciti, Patricia; Kelesidis, Iosif; Aufiero, Daniela; De Rosa, Veronica; Perna, Francesco; Fontana, Silvia; Mantzoros, Christos S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 22, 30.05.2006, p. 8481-8486.

Research output: Contribution to journalArticle

Chan, JL, Matarese, G, Shetty, GK, Raciti, P, Kelesidis, I, Aufiero, D, De Rosa, V, Perna, F, Fontana, S & Mantzoros, CS 2006, 'Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans', Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 22, pp. 8481-8486. https://doi.org/10.1073/pnas.0505429103
Chan, Jean L. ; Matarese, Giuseppe ; Shetty, Greeshma K. ; Raciti, Patricia ; Kelesidis, Iosif ; Aufiero, Daniela ; De Rosa, Veronica ; Perna, Francesco ; Fontana, Silvia ; Mantzoros, Christos S. / Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 22. pp. 8481-8486.
@article{b3d11d8df7104be183c9334a4e963f32,
title = "Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans",
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 ≈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.",
keywords = "Fasting, Reproductive",
author = "Chan, {Jean L.} and Giuseppe Matarese and Shetty, {Greeshma K.} and Patricia Raciti and Iosif Kelesidis and Daniela Aufiero and {De Rosa}, Veronica and Francesco Perna and Silvia Fontana and Mantzoros, {Christos S.}",
year = "2006",
month = "5",
day = "30",
doi = "10.1073/pnas.0505429103",
language = "English",
volume = "103",
pages = "8481--8486",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "22",

}

TY - JOUR

T1 - Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans

AU - Chan, Jean L.

AU - Matarese, Giuseppe

AU - Shetty, Greeshma K.

AU - Raciti, Patricia

AU - Kelesidis, Iosif

AU - Aufiero, Daniela

AU - De Rosa, Veronica

AU - Perna, Francesco

AU - Fontana, Silvia

AU - Mantzoros, Christos S.

PY - 2006/5/30

Y1 - 2006/5/30

N2 - 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 ≈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.

AB - 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 ≈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.

KW - Fasting

KW - Reproductive

UR - http://www.scopus.com/inward/record.url?scp=33744812000&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744812000&partnerID=8YFLogxK

U2 - 10.1073/pnas.0505429103

DO - 10.1073/pnas.0505429103

M3 - Article

C2 - 16714386

AN - SCOPUS:33744812000

VL - 103

SP - 8481

EP - 8486

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 22

ER -