The Good Neighbor: Coping With Insulin Resistance by Modulating Adipose Tissue Endothelial Cell Function.

Abstract

The prevalence of obesity is rising globally, and the United States has one of the highest obesity rates in the world: ≈17% of the young and >33% of adults are obese.1 Obesity is associated with chronic low-grade systemic inflammation, which is considered a critical underlying factor in the development of insulin resistance (IR).2 IR is a major risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease.3 In the development of obesity, white adipose tissue, particularly the abdominal adipose tissue, is the key site that mediates systemic inflammation and IR, though other organs, such as skeletal muscle and liver, have also been implicated.4 Adipose tissue is a highly vascularized organ where every adipocyte is connected to at least one capillary.5 To maintain normal adipose tissue function, the proper signaling between adipocytes and endothelial cells (ECs) from the surrounding vasculature is important.6 There is a growing body of evidence suggesting that EC dysfunction contributes to the pathogenesis of atherosclerosis, obesity, and T2DM.7,8 Therefore, it is of key interest to further study the role of the crosstalk between adipose tissue ECs and adipocytes in obesity-associated IR and to identify potential therapeutic targets for novel interventions. Recently, several reports suggested that microRNAs (miRs) are important mediators of the development of inflammation and IR in obese adipose tissue.9 Subsequently, numerous studies explored targeting specific miRs in diabetic complications to mitigate the pathological sequela of T2DM.9 Given these points, using miRs to modulate adipocyte–EC axis in adipose tissue may offer new tools to combat the growing epidemic of obesity and its associated comorbidities. Article, see p 810 Over the past 2 decades, several studies elucidated the underlying molecular mechanisms linking inflammation to obesity-associated IR. Hotamisligil et al10 was the first to demonstrate …