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FASEB J. 2016 Jan;30(1):241-51. doi: 10.1096/fj.15-276675. Epub 2015 Sep 11.

Adipose tissue adaptive response to trans-10,cis-12-conjugated linoleic acid engages alternatively activated M2 macrophages.

Author information

1
*Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Unité Mixte de Recherche en Santé 1166, Paris, France; INSERM, Unité Mixte de Recherche en Santé 1166, Nutriomics Team 6, Paris, France; Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Unité Mixte de Recherche U866, Université de Bourgogne, AgroSupDijon, Dijon, France; and Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Brussels, Belgium.
2
*Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Unité Mixte de Recherche en Santé 1166, Paris, France; INSERM, Unité Mixte de Recherche en Santé 1166, Nutriomics Team 6, Paris, France; Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Unité Mixte de Recherche U866, Université de Bourgogne, AgroSupDijon, Dijon, France; and Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Brussels, Belgium michele.guerre-millo@crc.jussieu.fr.

Abstract

In mice, nutritional supplementation with the trans-10,cis-12 isomer of linoleic acid (t10,c12-CLA) promotes lipoatrophy, hyperinsulinemia, and macrophage infiltration in white adipose tissue (WAT). We explored the dynamics of these interrelated responses over 2 consecutive 7 d periods of t10,c12-CLA administration and withdrawal. t10,c12-CLA down-regulated lipogenic and lipolytic gene expression and increased collagen deposition, but with no evidence of cross-linking. An abundant CD45(+) cell infiltrate, comprising prominently CD206(+)CD11c(-) macrophages, was found in WAT in association with an anti-inflammatory gene signature. Infiltration of natural killer (NK) and dendritic cells contributed to WAT's innate immune response to t10,c12-CLA. Less abundant adaptive immune cells colonized WAT, including B, NK T, γδ T, and αβ T cells. By contrast, T-regulatory cell abundance was not affected. Interruption of treatment allowed recovery of WAT mass and normalization of insulinemia, coincident with regain of WAT homeostasis owing to a coordinated reversion of genic, structural, and immune deregulations. These data revealed a striking resilience of WAT after a short-term metabolic injury induced by t10,c12-CLA, which relies on alternatively activated M2 macrophage engagement. In addition, the temporal links between variations in WAT alterations and insulinemia upon t10,c12-CLA manipulation strengthen the view that WAT dysfunctional status is critically involved in altered glucose homeostasis.

KEYWORDS:

fibrosis; hyperinsulinemia; lipoatrophy; lipophagy

PMID:
26362817
DOI:
10.1096/fj.15-276675
[Indexed for MEDLINE]

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