Educational Forum with Clinical Studies Current Science and Research

From the Institut National de la Santé et de la Recherche Médicale
(INSERM) (A.B., M.L.), Unité 858 & Université Toulouse III Paul
Sabatier, Institut de Médecine Moléculaire de Rangueil, Equipe No. 1
AVENIR, IFR31, BP84225, 31432 Toulouse, France; and UMR 5241 CNRS UPS
IFR31 (L.C.), IFR109 Institut Louis Bugnard, BP 84225, 31432 Toulouse
Cedex 4, France.

Correspondence to A. Bouloumié, Institut
National de la Santé et de la Recherche Médicale (INSERM), Unité 858
& Université Toulouse III Paul Sabatier, Institut de Médecine
Moléculaire de Rangueil, Equipe No. 1 AVENIR, IFR31, BP84225, 31432
Toulouse, France. E-mail anne. bouloumie@toulouse.inserm.fr

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 pathologies including 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 proinflammatory phenotype 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 expression of 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 a primary event that orchestrates the adipose tissue inflammation (Figure). This provocative and attractive idea poses a number of questions and requires further clinical investigations to validate its relevance in humans.