Adipose tissue remodeling in pathophysiology of obesity

Abstract

Purpose of review: Recent studies demonstrate that adipose tissue undergoes a continuous process of remodeling that is pathologically accelerated in the obese state. Contrary to earlier dogma, adipocytes die and are replaced by newly differentiated ones. This review will summarize recent advances of our knowledge of the mechanisms that regulate adipose tissue remodeling and highlight the influences of obesity, depot, and sex, as well as the relevance of rodent models to humans.

Recent findings: A substantial literature now points to the importance of dynamic changes in adipocyte and immune cell turnover, angiogenesis, and extracellular matrix remodeling in regulating the expandability and functional integrity of this tissue. In obesity, the macrophages are recruited, surrounding dead adipocytes and polarized toward an inflammatory phenotype. The number of dead adipocytes is closely associated with the pathophysiological consequences of obesity, including insulin resistance and hepatic steatosis. Further, there are substantial depot, sex and species differences in the extent of remodeling.

Summary: Adipose tissue undergoes a continuous remodeling process that normally maintains tissue health, but may spin out of control and lead to adipocyte death in association with the recruitment and activation of macrophages, and systemic insulin resistance.

Figure 1. The process of remodeling in obese mice

A) In well vascularized healthy adipose tissue, resident regulatory CD4+ T cells and M2 macrophages are present and remodel the tissue, restricting inflammation and improving insulin sensitivity. B) With increasing adipocyte hypertrophy, the ratio of CD8+/CD4+ T cells increases and this may help recruit macrophages. C) With the further expansion of adipose tissue, more macrophages acquire a proinflammatory, M1 phenotype, especially those in CLS around dead or dying adipocytes. Coincidentally, restrictions of blood flow and hypoxia stimulate inflammatory cytokine production and worsen adipocyte dysfunction. D) With time, macrophages clear out the dead adipocytes which are replaced by the newly-differentiated, insulin sensitive adipocytes.