Mechanisms of inflammation amplification through adipocyte-macrophage interactions

Abstract

Obesity is associated with numerous health impairments, including type 2 diabetes mellitus and coronary artery disease. Adipose tissue in cases of obesity shows infiltration of immune cells such as macrophages which induce chronic inflammation, which, in turn, can lead to pathological conditions such as insulin resistance and atherosclerosis. We comprehensively analyzed the factors involved in chronic adipose tissue inflammation by co-culturing adipocytes and macrophages. We focused on CCL19, a chemokine whose expression was significantly elevated in adipocytes co-cultured with macrophages. We generated Ccl19 knock-in (KI) mice specifically overexpressing CCL19 in adipocytes, and demonstrated that activation of CCL19 signaling in adipose tissue amplifies inflammation, impairs lipid metabolism and energy regulation, and contributes to glucose intolerance. The differences observed between the Ccl19KI and wild-type mice were most pronounced in the groups fed a 40% high-fat diet as compared with a normal diet and the 60% high-fat diet. Our results suggest that mild obesity increases the systemic effects of local inflammation. In mild obesity, which is common among Japanese individuals, periodontitis can be amplified to a systemic level through the activation of inflammatory signaling pathways mediated by interactions between adipocytes and immune cells such as macrophages in the adipose tissue.