title: Adipose tissue adaptive response to trans-10,cis-12-conjugated linoleic acid engages alternatively activated M2 macrophages.
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.
authors.affiliation: *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.
authors.forename: Maria
authors.initials: M
authors.lastname: Pini
authors.affiliation: *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.
authors.forename: Sothea
authors.initials: S
authors.lastname: Touch
authors.affiliation: *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.
authors.forename: Hélène
authors.initials: H
authors.lastname: Poirier
authors.affiliation: *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.
authors.forename: Elise
authors.initials: E
authors.lastname: Dalmas
authors.affiliation: *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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Niot
authors.affiliation: *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.
authors.forename: Christine
authors.initials: C
authors.lastname: Rouault
authors.affiliation: *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.
authors.forename: Céline
authors.initials: C
authors.lastname: Druart
authors.affiliation: *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.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Delzenne
authors.affiliation: *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.
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.affiliation: *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.
authors.forename: Sébastien
authors.initials: S
authors.lastname: André
authors.affiliation: *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.
authors.forename: Michèle
authors.initials: M
authors.lastname: Guerre-Millo
mesh_terms: D000222:Adaptation, Physiological; D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D044243:Linoleic Acids, Conjugated; C496197:trans-10,cis-12-conjugated linoleic acid
keywords: fibrosis; hyperinsulinemia; lipoatrophy; lipophagy