Persistence of inflammatory adipose tissue immune cells despite weight loss in obese mice

Obesity causes dramatic changes to the adipose tissue immune environment including the recruitment and activation of macrophages. The inflammatory polarization of these cells is thought to play a critical role in the severity of insulin resistance associated with obesity. Weight loss can improve insulin resistance, but little is known concerning the effects of weight loss on immune activity in adipose. 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 structural changes were evaluated by histology. Leukocyte populations were analyzed by flow cytometry, including sorting and comparing cytokine expression of adipose tissue macrophages before and after weight loss. Weight loss improved glucose tolerance and reduced serum insulin. However, extensive adipose fibrosis developed during weight loss and was associated with macrophage accumulation. Analysis of adipose macrophages after weight loss showed they retained an inflammatory gene expression profile similar to those found during obesity. These macrophages were derived primarily from older cells present during obesity. These macrophages were maintained though high proliferation and low apoptosis. The data indicate that inflammatory activation of adipose macrophages is not sufficient for whole body metabolic dysfunction, but the retained macrophages may promote adipose tissue fibrosis while impacting adipocyte health and function.