Adipocytes, like their progenitors, contribute to inflammation of adipose tissues through promotion of Th-17 cells and activation of monocytes, in obese subjects

ABSTRACT

Recently, we have reported that adipose tissue-derived stem cells (ASC) harvested from obese donors induce a pro-inflammatory environment when co-cultured with peripheral blood mononuclear cells (MNC), with a polarization of T cells toward the Th17 cell lineage, increased secretion of IL-1β and IL-6 pro-inflammatory cytokines, and down-regulation of Th1 cytokines, such as IFNγ and TNFα. However, whether differentiated adipocytes, like the aforementioned ASC, are pro-inflammatory in obese subject AT remained to be investigated. Herein, we isolated ASC from AT of obese donors and differentiated them into adipocytes, for either 8 or 14 d. We analyzed their capacity to activate blood MNC after stimulation with phytohemagglutinin A (PHA), or not, in co-culture assays. Our results showed that co-cultures of MNC with adipocytes, like with ASC, increased IL-17A, IL-1β, and IL-6 pro-inflammatory cytokine secretion. Moreover, like ASC, adipocytes down-regulated TNFα secretion by Th1 cells. As adipocytes differentiated from ASC of lean donors also promoted IL-17A secretion by MNC, an experimental model of high-fat versus chow diet mice was used and supported that adipocytes from obese, but not lean AT, are able to mediate IL-17A secretion by PHA-activated MNCs. In conclusion, our results suggest that, as ASC, adipocytes in obese AT might contribute to the establishment of a low-grade chronic inflammation state.

KEYWORDS:

• adipose-tissue derived stem cells
• ASC
• blood mononuclear cells
• IL-17A
• subcutaneous adipose tissue
• Th17

Abbreviations

ASC	=	adipose-tissue derived mesenchymal stem cells
AT	=	adipose tissue
AC	=	adipose cells
SVF	=	stromal vascular fraction
IL-17A	=	interleukin-17A
MNC	=	mononuclear cells

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgment

We thank Dr. A. Mey for providing part of the ASC used in this study.

Funding

This work was supported by the INSERM institute, Hospices Civils de Lyon and research grants from “Fondation de l'Avenir” and “Fondation Chèque Dejéuner” to Assia. Eljaafari. MC was supported by a PhD scholarship from the Rhone-Alpes region.