Role of Distinct Fat Depots in Metabolic Regulation and Pathological Implications.

Abstract

People suffering from obesity and associated metabolic disorders including diabetes are increasing exponentially around the world. Adipose tissue (AT) distribution and alteration in their biochemical properties play a major role in the pathogenesis of these diseases. Emerging evidence suggests that AT heterogeneity and depot-specific physiological changes are vital in the development of insulin resistance in peripheral tissues like muscle and liver. Classically, AT depots are classified into white adipose tissue (WAT) and brown adipose tissue (BAT); WAT is the site of fatty acid storage, while BAT is a dedicated organ of metabolic heat production. The discovery of beige adipocyte clusters in WAT depots indicates AT heterogeneity has a more central role than hither to ascribed. Therefore, we have discussed in detail the current state of understanding on cellular and molecular origin of different AT depots and their relevance toward physiological metabolic homeostasis. A major focus is to highlight the correlation between altered WAT distribution in the body and metabolic pathogenesis in animal models and humans. We have also underscored the disparity in the molecular (including signaling) changes in various WAT tissues during diabetic pathogenesis. Exercise-mediated beneficial alteration in WAT physiology/distribution that protects against metabolic disorders is evolving. Here we have discussed the depot-specific biochemical adjustments induced by different forms of exercise. A detailed understanding of the molecular details of inter-organ crosstalk via substrate utilization/storage and signaling through chemokines provide strategies to target selected WAT depots to pharmacologically mimic the benefits of exercise countering metabolic diseases including diabetes.