Adipocytes Secrete Leukotrienes
Contribution to Obesity-Associated Inflammation and Insulin Resistance in Mice
- Isabelle Mothe-Satney1,2,
- Chantal Filloux1,2,
- Hind Amghar1,2,
- Catherine Pons2,3,
- Virginie Bourlier4,5,
- Jean Galitzky4,5,
- Paul A. Grimaldi1,2,
- Chloé C. Féral2,3,
- Anne Bouloumié4,5,
- Emmanuel Van Obberghen1,2,6 and
- Jaap G. Neels1,2⇓
- 1INSERM, U907, Nice, France
- 2Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France
- 3Avenir Team, INSERM, U634, Nice, France
- 4“Stroma-Vascular Cells of Adipose Tissue” Team, Institute of Metabolic and Cardiovascular Diseases, INSERM, U1048, Toulouse, France
- 5Université Paul Sabatier, University of Toulouse, Toulouse, France
- 6Biochemistry Laboratory, Pasteur Hospital, Nice, France
- Corresponding author: Jaap G. Neels, .
I.M.-S. and C.F. contributed equally to this work.
Leukotrienes (LTs) are potent proinflammatory mediators, and many important aspects of innate and adaptive immune responses are regulated by LTs. Key members of the LT synthesis pathway are overexpressed in adipose tissue (AT) during obesity, resulting in increased LT levels in this tissue. We observed that several mouse adipocyte cell lines and primary adipocytes from mice and humans both can secrete large amounts of LTs. Furthermore, this production increases with a high-fat diet (HFD) and positively correlates with adipocyte size. LTs produced by adipocytes play an important role in attracting macrophages and T cells in in vitro chemotaxis assays. Mice that are deficient for the enzyme 5-lipoxygenase (5-LO), and therefore lack LTs, exhibit a decrease in HFD-induced AT macrophage and T-cell infiltration and are partially protected from HFD-induced insulin resistance. Similarly, treatment of HFD-fed wild-type mice with the 5-LO inhibitor Zileuton also results in a reduction of AT macrophages and T cells, accompanied by a decrease in insulin resistance. Together, these findings suggest that LTs represent a novel target in the prevention or treatment of obesity-associated inflammation and insulin resistance.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1455/-/DC1.
- Received October 14, 2011.
- Accepted March 22, 2012.
- © 2012 by the American Diabetes Association.
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