Adipocytes Secrete Leukotrienes

Contribution to Obesity-Associated Inflammation and Insulin Resistance in Mice

  1. Jaap G. Neels1,2
  1. 1INSERM, U907, Nice, France
  2. 2Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France
  3. 3Avenir Team, INSERM, U634, Nice, France
  4. 4“Stroma-Vascular Cells of Adipose Tissue” Team, Institute of Metabolic and Cardiovascular Diseases, INSERM, U1048, Toulouse, France
  5. 5Université Paul Sabatier, University of Toulouse, Toulouse, France
  6. 6Biochemistry Laboratory, Pasteur Hospital, Nice, France
  1. Corresponding author: Jaap G. Neels, jaap.neels{at}unice.fr.
  1. I.M.-S. and C.F. contributed equally to this work.

Abstract

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.

Footnotes

  • Received October 14, 2011.
  • Accepted March 22, 2012.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

| Table of Contents

This Article

  1. Diabetes vol. 61 no. 9 2311-2319
  1. Supplementary Data
  2. All Versions of this Article:
    1. db11-1455v1
    2. 61/9/2311 most recent