Inflammation in obesity-related diseases.

ADIPOSE TISSUE---A PRIMARY IN VIVO SITE OF INFLAMMATION IN OBESITY Adipose tissue comprises not only adipocytes but also a stromovascular cell fraction. This stromovascular cell fraction consists of a diverse population of lymphocytes, fibroblasts, endothelial and stromal cells, and preadipocytes, which along with adipocytes, serve as a rich source of cytokines and adipokines. Adipocytes themselves are related closely to fibroblasts and macrophages, and in fact, evidence supports their ability to transdifferentiate into macrophages in vivo. Adipose tissue should, therefore, in addition to its role as a storage depot for lipid, be considered an immune organ, and in this capacity, it is a primary in vivo site of inflammation in obesity. Expression of positive regulators of inflammation is increased in subcutaneous adipose tissue from obese humans and mice, whereas calorie restriction causes a reversion of the adipose tissue transcriptome toward that similar to lean subjects, with downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. Furthermore, the magnitude of the ‘‘inflammatory shift’’ in the adipose tissue transcriptome correlates with the presence and magnitude of obesity-related comorbidities, including insulin resistance and steatohepatitis. Adding to its complexity of function, different anatomic depots of adipose tissue manifest distinct metabolic properties. Although excess subcutaneous adipose tissue (SAT) imparts risk, excess visceral adipose tissue (VAT) is even more strongly predictive of obesityrelated comorbidities and long-term mortality. Visceral lipectomy in rodents and in a single trial in human bariatric surgery patients seems to ameliorate insulin resistance, whereas subcutaneous