Cited by 287Adipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and ObesityCytokine Signaling Pathways and Interactions

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IL-1 Receptor Antagonist Serum Levels Are Increased in Human Obesity: A Possible Link to the Resistance to Leptin?

Meier, Christoph A., Bobbioni, Elisabetta, Gabay, Cem, Assimacopoulos-Jeannet, Françoise, Golay, Alain, Dayer, Jean-Michel·2002·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jcem.87.3.8351

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Abstract

We have recently shown that human monocytic cells express functional leptin receptors and that leptin is capable of inducing the expression and secretion of the IL-1 receptor antagonist (IL-1Ra). Although IL-1Ra has anti-inflammatory and possibly anti-atherogenic properties, it has also been shown to antagonize the action of leptin at the hypothalamic level in rodents, thereby inducing leptin resistance. We have therefore examined whether IL-1Ra levels are increased in human hyperleptinemic conditions, such as obesity. To this end, we measured serum IL-1Ra levels in 20 morbidly obese nondiabetic subjects [body mass index (BMI), 45 +/- 6 kg/m(2); serum leptin, 52 +/- 20 ng/ml] as well as in 10 age- and sex-matched lean controls (BMI, 22 +/- 2 kg/m(2); serum leptin, 7 +/- 4 ng/ml). Serum IL-1Ra concentrations proved to be elevated 6.5-fold in the obese subjects, and they were positively correlated in a linear manner with the leptin levels (r(2) = 0.34; P = 0.01), although lean body mass (LBM) and the insulin resistance index were even better predictors of IL-1Ra levels (r(2) = 0.45 and 0.58, respectively; P < 0.01). Six months after 15 of the 20 obese subjects had undergone bypass surgery for their morbid obesity, their mean BMI and leptin levels decreased to 33 +/- 7 kg/m(2) and 18 plus minus 12 ng/ml, respectively. This change in leptin concentrations was associated with a significant reduction in IL-1Ra levels (P < 0.02). However, there was a better correlation between the decrease in IL-1Ra level and the change in LBM than with the reduction in leptin levels, indicating that leptin is not the sole determinant of circulating IL-1Ra in obesity. In summary, we demonstrate that IL-1Ra levels are highly elevated in human obesity and that its concentrations decrease after weight loss from bypass surgery. However, LBM and insulin resistance are better predictors of serum IL-1Ra concentrations than are leptin levels, suggesting that additional metabolic factors control the secretion of this cytokine antagonist. Although the immunological consequences of this alteration remain unknown, it is tempting to speculate that the obesity-related increase in IL-1Ra might contribute to the central resistance to leptin in obese patients, similar to the inhibition of the hypothalamic signaling of leptin by IL-1Ra in rodents.

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Authors: Meier, C. A., Bobbioni, E., Gabay, C., Assimacopoulos-Jeannet, F., Golay, A., & Dayer, J.-M.
Affiliations: University Hospital of Geneva (CH)
Corresponding author: Meier, Christoph A.
ORCID: Meier, Christoph A.
Gabay, Cem
Golay, Alain
Dayer, Jean-Michel
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2002-03
Volume: 87
Issue: 3
Pages: 1184-1188
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jcem.87.3.8351
OpenAlex: W2015072700
Cited by: 287
References: 17
Citations by year: 2026: 3 · 2025: 3 · 2024: 8 · 2023: 13 · 2022: 13 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 13 · 2017: 7 · 2016: 7 · 2015: 15 · 2014: 15 · 2013: 14 · 2012: 13
FWCI: 8.79
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: interleukin-1 receptor antagonist, obesity, leptin resistance, leptin, morbid obesity, weight loss, insulin resistance, lean body mass, serum cytokine levels, leptin receptor, monocytic cells, anti-inflammatory cytokines, atherogenesis, body mass index, cytokine antagonists
MeSH terms: Adult, Female, Humans, Middle Aged, Obesity, Obesity, Morbid, Osmolar Concentration, Postoperative Period, Reference Values, Sialoglycoproteins, Gastric Bypass, Leptin, Interleukin 1 Receptor Antagonist Protein

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IL-1 Receptor Antagonist Serum Levels Are Increased in Human Obesity: A Possible Link to the Resistance to Leptin?

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