Macrophage phenotype and bioenergetics are controlled by oxidized phospholipids identified in lean and obese adipose tissue

Abstract

Significance Adipose tissue macrophages (ATMs) maintain adipose tissue homeostasis. However, during obesity ATMs become inflammatory, resulting in impaired adipose tissue function. Oxidative stress increases during obesity, which is thought to contribute to adipose tissue inflammation. To date, the connection between oxidative stress and adipose tissue inflammation remain unclear. In this study, we identify two classes of phospholipid oxidation products in lean and obese adipose tissue, which polarize macrophages to an antioxidant or proinflammatory state, respectively. Furthermore, we show that these phospholipids differently affect macrophage cellular metabolism, reflecting the metabolisms of ATMs found in lean and obese adipose tissue. Identification of pathways controlling ATM metabolism will lead to novel therapies for insulin resistance.