Obesity, and more specifically accumulation of adipose tissue in the visceral and subcutaneous abdominal locations, is a major risk factor for the development of cardiovascular pathologiesincluding hypertension and atherosclerosis, as well as metabolic disorders such as type 2 diabetes. During recent years, "metaflammation" or metabolically-triggered inflammation1 has emerged as a key process involved in the clustering of those conditions. Although several metabolically active organs such as the liver, muscle, and, recently, the intestine2 certainly play major roles, the white adipose tissue appears as a central and primary player as both a source and site of inflammation. Accumulation of adipose tissue macrophages (ATMs) has been well-described in obese conditions in mice and humans.3–5 Moreover, the ATM proinflammatoryphenotype has been linked to the development of insulin resistance in mice,4 although the exact nature of the proinflammatory myeloid cells, ie, macrophages or dentritic cells, remains to be determined.6 Nevertheless, the causal link between inflammation and insulin resistance was further strengthened by the specific knock-out of the inflammation coordinator IkappaB kinase beta of myeloid cells, which gave protection against insulin resistance.7 The study of Kintscher and al in this issue8 extends those original observations to cells of adaptative immunity. The authors suggest that the accumulation of T-lymphocytes, assessed mainly through gene expression analyses and immunohistochemistry, occurs in the perigonadal adipose tissue of mice on a high-fat diet before the accumulation of macrophages. Moreover, the increased expressionof T-lymphocyte markers was concomitant with the initiation of insulin resistance characterized by a reduction in systemic glucose tolerance and insulin sensitivity, at least compared with counterpart animals that were 5 weeks younger. Given these new findings in rodents, the authors suggest that early lymphocyte infiltration of the adipose tissue might be considered as aprimary event that orchestrates the adipose tissue inflammation (Figure). This provocative and attractive idea poses a number of questions and requires further clinical investigations tovalidate its relevance in humans.
Xanya Sofra Weiss
Xanya Sofra Weiss
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