A role for 5-lipoxygenase products in obesity-associated inflammation and insulin resistance

Abstract

There is a growing amount of evidence that obesity-induced low-grade inflammation is an important causative link between obesity and many of its associated pathologies such as type 2 diabetes and atherosclerosis. In the quest to identify the triggers of obesity-associated inflammation of adipose tissue, our laboratory recently demonstrated that adipocytes can secrete leukotrienes, and that these pro-inflammatory lipid mediators contribute to obesity-associated inflammation and insulin resistance in mice. Together with other recent studies, our recent findings identify an important role for the enzyme 5-lipoxygenase and its products in the induction and resolution of adipose tissue inflammation. Therefore, pharmaceutical approaches that target this enzyme or its products should be considered as novel treatments aimed at preventing or resolving obesity-induced inflammation and its associated pathologies.

Keywords: 5-lipoxygenase; adipose tissue; inflammation; insulin resistance; obesity.

Figure 1. Adipose tissue lipoxin A4 levels. Lipoxin A4 levels in epi-WAT derived from NC- and HFD-fed wild-type mice and HFD-fed wild-type mice treated p.o. daily for a 2-week period with either vehicle (10% DMSO) or zileuton (100 mg/kg). Data are expressed as mean ± SEM (n ≥ 6). **p < 0.01 compared with NC; ^##p < 0.01 compared with HFD + veh.