Adipocytes secrete leukotrienes: contribution to obesity-associated inflammation and insulin resistance in mice.

Isabelle Mothe-Satney 1 Chantal Filloux 1 Hind Amghar 1 Catherine Pons 2 Virginie Bourlier 3 Jean Galitzky 3 Paul Grimaldi 1 Chloé Féral 2 Anne Bouloumié 3 Emmanuel Van Obberghen 1, 4 Jaap Neels 1, *
* Auteur correspondant
1 Dysfonctions métaboliques et diabètes: Mécanismes et approches thérapeutiques
2 CD98 Heavy Chain: a key component of the regulation of integrins in wound healing and skin tumorigenesis?
3 Inserm U1048, équipe cellules de la fraction stroma-vasculaire du tissu adipeux
I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
4 CHU - Hôpital Pasteur [Nice]
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.
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Article dans une revue
Diabetes, American Diabetes Association, 2012, 61 (9), pp.2311-9. 〈10.2337/db11-1455〉
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http://www.hal.inserm.fr/inserm-00726172
Contributeur : Marie Francoise Simon <>
Soumis le : mercredi 29 août 2012 - 10:44:59
Dernière modification le : jeudi 4 octobre 2018 - 09:50:10

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Isabelle Mothe-Satney, Chantal Filloux, Hind Amghar, Catherine Pons, Virginie Bourlier, et al.. Adipocytes secrete leukotrienes: contribution to obesity-associated inflammation and insulin resistance in mice.. Diabetes, American Diabetes Association, 2012, 61 (9), pp.2311-9. 〈10.2337/db11-1455〉. 〈inserm-00726172〉

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