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

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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Crossref · 10.1210/jcem.87.3.8351

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  • A strong association between extent of weight loss after bariatric surgery and amount of bone loss has been documented by most but not all studies.

    “A strong association between extent of weight loss after bariatric surgery and amount of bone loss has been documented bymost40, 45, 51-53, 62, 67 but not all studies.63”

    From Bone loss after bariatric surgery: causes, consequences, and management (2014) · cites this paper as [45]

  • In healthy younger and older human subjects, dietary advanced glycation end products, but not energy intake, correlated with serum advanced glycation end product levels and markers of oxidative stress, which in turn correlated with serum C-reactive protein concentration and insulin resistance.

    “In healthy younger (aged , 45 years) and older (aged .60 years) human subjects, dietary AGE, but not energy intake, correlated with serum AGE levels and markers of oxidative stress (8-isoprostanes), which in turn correlated with serum CRP concentration and insulin resistance (514 -521) (Table 12).”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [514]

  • Pro-inflammatory transcription factors, inflammatory markers including CRP, IL-6, IL-8, TNF-a and matrix metalloproteinase, and endothelial dysfunction markers VCAM-1, ICAM-1 and E-selectin are elevated in response to acute and persistent hyperglycaemia.

    “Accordingly, pro-inflammatory transcription factors, inflammatory markers including CRP, IL-6, IL-8, TNF-a and matrix metalloproteinase and markers of endothelial dysfunction VCAM-1, ICAM-1 and E-selectin have been observed to be elevated in response to acute and persistent hyperglycaemia (474,475,514,521,653,662,670,671) .”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [514]

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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
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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Oncology › 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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