CoChat
Sign Up
Cited by 56Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesCytokine Signaling Pathways and Interactions

Recombinant Methionyl Human Leptin Administration Activates Signal Transducer and Activator of Transcription 3 Signaling in Peripheral Blood Mononuclear Cells in Vivo and Regulates Soluble Tumor Necrosis Factor-α Receptor Levels in Humans with Relative Leptin Deficiency

Chan, Jean L., Moschos, Stergios J., Bullen, John, Heist, Kathleen, Li, Xian, Kim, Young-Bum, Kahn, Barbara B., Mantzoros, Christos S.·2005·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2004-1823
Open this paper in CoChat — free account

Abstract

Studies of congenital complete leptin deficiency in animals and humans support a role for leptin in regulating immune function. Whether acquired relative leptin deficiency affects immunological parameters in healthy humans remains unknown. We thus used experimental models of relative leptin deficiency and recombinant methionyl human leptin (r-metHuLeptin) administration in humans to investigate whether r-metHuLeptin would activate signaling pathways in peripheral blood mononuclear cells (PBMCs) and whether acquired relative leptin deficiency and/or increasing circulating leptin levels into the physiologic range would change PBMC subpopulations and cytokines important in the T-helper cell and systemic immune responses. We found that r-metHuLeptin administration to healthy humans activates signal transducer and activator of transcription-3 signaling in PBMCs in vivo. Neither short-term leptin deficiency, induced by 3-d complete fasting, nor physiologic r-metHuLeptin replacement for the same period of time had a major effect on PBMC subpopulations or serum cytokines in healthy men. In contrast, normalizing serum leptin levels over 8 wk in lean women with relative leptin deficiency for 5.1 +/- 1.4 yr (mean +/- se) due to chronic energy deficit increased soluble TNFalpha receptor levels, indicating activation of the TNFalpha system. These findings suggest that relative leptin deficiency due to more long-term energy deprivation is associated with defects in immunological parameters that may be corrected with exogenous r-metHuLeptin administration. Further studies are warranted to assess the implications of acquired relative hypoleptinemia and/or r-metHuLeptin administration on the immunosuppression associated with energy- and leptin-deficient states in humans.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1210/jc.2004-1823

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Interventional studies show a role for leptin in regulating the immune system in states of leptin deficiency, but not leptin excess as seen in obesity.

    “Interventional studies investigating the effect of leptin administration to persons with leptin deficiency compared with leptin sufficiency or leptin excess could clearly show a role for leptin in regulating the immune system in states of leptin deficiency, but not leptin excess, as seen in obesity (22,27,31).”

    From Leptin in humans: lessons from translational research (2009) · cites this paper as [31]

  • r-metHuLeptin administered in replacement doses to healthy subjects after starvation for 72 h prevented the starvation-induced reduction of CD4+CD45RA+ peripheral mononuclear blood cells.

    “r-metHuLeptin administered in replacement doses to healthy subjects (after starvation for 72 h) prevented the starvation-induced reduction of CD4 1 CD45RA 1 peripheral mononuclear blood cells (31).”

    From Leptin in humans: lessons from translational research (2009) · cites this paper as [31]

  • Relative leptin deficiency because of long-term energy deprivation is associated with defects in immunologic variables that may be corrected with exogenous r-metHuLeptin administration.

    “Similar to congenital leptin deficiency, relative leptin deficiency because of long-term energy deprivation is associated with defects in immunologic variables that may be corrected with exogenous r-metHuLeptin administration: Leptin replacement therapy alters circulating cytokine concentrations in women with hypothalamic amenorrhea who present with chronic relative leptin deficiency resulting”

    From Leptin in humans: lessons from translational research (2009) · cites this paper as [31]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Chan, J. L., Moschos, S. J., Bullen, J., Heist, K., Li, X., Kim, Y.-B., Kahn, B. B., & Mantzoros, C. S.
Affiliations
Beth Israel Deaconess Medical Center (US)
Corresponding author
Mantzoros, Christos S.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2005-03
Volume
90
Issue
3
Pages
1625-1631
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2004-1823
OpenAlex
W2057788834
Cited by
56
References
46
Citations by year
2024: 1 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 5
FWCI
2.29
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Vlaamse regering
  • U.S. Public Health Service (R0-158785)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK43051, R01DK043051)
  • National Center for Research Resources (M01-RR-01032, M01RR001032)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
leptin replacement therapy, STAT3 signaling, peripheral blood mononuclear cells, soluble TNF-alpha receptor, immune function, negative energy balance, fasting, immunosuppression, cytokines, T helper cells
MeSH terms
Adult, DNA-Binding Proteins, Female, T-Lymphocytes, Helper-Inducer, Humans, Male, Milk Proteins, Phosphorylation, Tumor Necrosis Factor-alpha, Signal Transduction, Trans-Activators, Cytokines, Proto-Oncogene Proteins c-bcl-2, Leptin, Mitogen-Activated Protein Kinases, STAT1 Transcription Factor, STAT3 Transcription Factor, STAT5 Transcription Factor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review