Adipose Tissue Is a Major Source of Interleukin-1 Receptor Antagonist
Upregulation in Obesity and Inflammation
- Cristiana E. Juge-Aubry1,
- Emmanuel Somm1,
- Vittorio Giusti2,
- Agnès Pernin1,
- Rachel Chicheportiche3,
- Chantal Verdumo2,
- Françoise Rohner-Jeanrenaud1,
- Danielle Burger3,
- Jean-Michel Dayer3 and
- Christoph A. Meier1
- 1Endocrine Unit, Division of Endocrinology, Diabetes and Nutrition, Department of Internal Medicine, University Hospital, Geneva, Switzerland
- 2Division of Endocrinology, Diabetology, and Metabolism, Department of Medicine, University Hospital, Lausanne, Switzerland
- 3Hans Wilsdorf Laboratory, Division of Immunology and Allergy, Department of Internal Medicine, University Hospital, Geneva, Switzerland
Abstract
The secreted form of the interleukin-1 receptor antagonist (IL-1Ra) is an acute-phase protein intervening in the counterregulation of inflammatory processes. We previously showed that this cytokine antagonist is upregulated in the serum of obese patients, correlating with BMI and insulin resistance. In this study, we examined the expression pattern of IL-1Ra and showed that it is highly expressed not only in liver and spleen, but also in white adipose tissue (WAT), where it is upregulated in obesity. In WAT of obese humans, IL-1Ra was also markedly increased. Moreover, human WAT explants secreted IL-1Ra into the medium, a process that could be stimulated fivefold by interferon-β. Finally, lipopolysaccharide administration induced a long-lasting expression of IL-1Ra in mouse WAT, suggesting that adipose tissue is an important source of IL-1Ra in both obesity and inflammation. In summary, we demonstrated that WAT is one of the most important sources of IL-1Ra quantitatively, suggesting that this tissue could represent a novel target for anti-inflammatory treatment. Moreover, it can be speculated that IL-1Ra, whose production is markedly increased in WAT in obese individuals, contributes further to weight gain because of its endocrine and paracrine effects on the hypothalamus and adipocytes, respectively.
Footnotes
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Address correspondence and reprint requests to Dr. Christoph A. Meier, Endocrine Unit, University Hospital Geneva, 24, rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. E-mail: christoph.meier{at}medecine.unige.ch.
Received for publication 6 January 2003 and accepted in revised form 12 February 2003.
C.E.J.-A. and E.S. contributed equally to this work.
BAT, brown adipose tissue; FBS, fetal bovine serum; HT, hypothalamus; icIL-1Ra, intracellular IL-1Ra; IFN-β, interferon-β; IL, interleukin; IL-1Ra, interleukin-1 receptor antagonist; LPS, lipopolysaccharide; PMA, phorbol myristate acetate; PPAR-γ, peroxisome proliferator−activated receptor-γ; sIL-1Ra, secreted IL-1Ra; TNF-α, tumor necrosis factor-α; WAT, white adipose tissue; WATe, epididymal WAT; WATi, inguinal WAT
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