Impact of weight loss on obese adipose tissue immune cell function (CAM1P.154)

Abstract

Abstract Obesity induces inflammation in adipose tissue involving the recruitment and activation of macrophages, CD8+ and CD4+ T cells. These cells play a critical role in the development of insulin resistance seen with obesity. Weight loss can improve insulin resistance and health, but little is known concerning the effects of weight loss on immune activity in adipose tissue. Diet switch from a 60% high-fat diet to 13% normal-fat diet was used to induce weight loss in diet-induced obese C57Bl/6 mice. Adipose tissue fibrosis and macrophage accumulation was evaluated by histology. Leukocyte populations were analyzed by flow, including sorting and cytokine expression comparisons of adipose tissue macrophages before and after weight loss. Weight loss improved glucose tolerance and reduced serum insulin. However extensive adipose fibrosis developed after diet switch and was associated with macrophage accumulation. Analysis of macrophages after weight loss showed they retained a pro-inflammatory gene expression profile and had high surface marker expression of T cell co-stimulatory markers, similar to macrophages found in obese adipose tissue. These adipose macrophages were comprised of both old and newly recruited cells that continued to be activated after weight loss. The continued inflammatory activation of leukocytes after weight loss may help explain the variation seen in metabolic improvements and long-term weight management of patients in response to weight loss interventions.