Abstract
Low-grade inflammation in adipose tissue is recognized as a critical event in the development of obesity-related co-morbidities. This chronic inflammation is powerfully augmented through the infiltration of macrophages, which together with adipocytes, perpetuate a vicious cycle of inflammatory cell recruitment and secretion of free fatty acids and deleterious adipokines that predispose to greater incidence of metabolic complications. In the last decade, many factors have been identified to contribute to mounting unresolved inflammation in obese adipose tissue. Among them, pro-inflammatory lipid mediators (i.e., leukotrienes) derived from the omega-6 polyunsaturated arachidonic acid have been shown to play a prominent role. Of note, the same lipid mediators that initially trigger the inflammatory response also signal its termination by stimulating the formation of anti-inflammatory signals. Resolvins and protectins derived from the omega-3 polyunsaturated docosahexaenoic and eicosapentaenoic acids have emerged as a representative family of this novel class of autacoids with dual anti-inflammatory and pro-resolving properties that act as “stop-signals” of the inflammatory response. This review discusses the participation of these endogenous autacoids in the resolution of adipose tissue inflammation, with a special emphasis in the amelioration of obesity-related metabolic dysfunctions, namely insulin resistance and non-alcoholic fatty liver disease.
Highlights
This review discusses the participation of these endogenous autacoids in the resolution of adipose tissue inflammation, with a special emphasis in the amelioration of obesity-related metabolic dysfunctions, namely insulin resistance and non-alcoholic fatty liver disease
We have recently demonstrated that the production of specialized pro-resolving mediators (SPM) (i.e., RvD1 and PD1 and the metabolic precursors 14-HDHA, 17-HDHA, 18-HEPE) is deficient in inflamed obese adipose tissue (Clària et al, 2012)
These investigators first noticed that docosahexaenoic acid (DHA) did not modify the total number of macrophages in obese adipose tissue, but markedly reduced the percentage of CD11bhigh/F4/80high expressing cells in parallel with the emergence of low-expressing CD11b/F4/80 macrophages, suggesting a phenotypic switch in macrophage polarization. These investigators further demonstrated that DHA and RvD1 up-regulated a complete panel of M2 markers including IL-10, CD206, resistin-like molecule (RELM)-α, and Ym1, and remarkably stimulated arginase 1 expression while promoting non-phlogistic macrophage phagocytosis and attenuating IFNγ/LPS-induced Th1 cytokine secretion (Titos et al, 2011). These results were in agreement with those reported by Hellmann et al (2011), who showed the ability of RvD1 to improve insulin resistance in obese-diabetic mice, by reducing macrophage F4/80+CD11c+ cell accumulation and increasing the percentage of positive F4/80 cells expressing the M2 marker Mgl-1 in adipose tissue
Summary
This review discusses the participation of these endogenous autacoids in the resolution of adipose tissue inflammation, with a special emphasis in the amelioration of obesity-related metabolic dysfunctions, namely insulin resistance and non-alcoholic fatty liver disease. RESOLUTION OF ADIPOSE TISSUE INFLAMMATION IN OBESITY Abdominal obesity and insulin resistance are the predominant underlying risk factors for the metabolic syndrome and related co-morbidities such as type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease (Elks and Francis, 2010).
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