Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study.
BACKGROUND
Bariatric surgery is associated to improvements in obesity-associated comorbidities thought to be mediated by a decrease of adipose inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood.


RESULTS
We analyzed RNA-seq expression profiles in adipose tissue from 22 obese women before and 3 months after surgery. Of 15,972 detected genes, 1214 were differentially expressed after surgery at a 5% false discovery rate. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, 26 modules of coexpressed genes were identified. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue. A first module reflecting a non-specific signature of innate immune cells, mainly macrophages, was highly conserved after surgery with the exception of DUSP2 and CD300C. A second module reflected the adaptive immune response elicited by T lymphocytes; after surgery, a disconnection was observed between genes involved in T-cell signaling and mediators of the signal transduction such as CXCR1, CXCR2, GPR97, CCR7 and IL7R. A third module reflected neutrophil-mediated inflammation; after surgery, several genes were dissociated from the module, including S100A8, S100A12, CD300E, VNN2, TUBB1 and FAM65B. We also identified a dense network of 19 genes involved in the interferon-signaling pathway which was strongly preserved after surgery, with the exception of DDX60, an antiviral factor involved in RIG-I-mediated interferon signaling. A similar loss of connection was observed in lean mice compared to their obese counterparts.


CONCLUSIONS
These results suggest that improvements of the inflammatory state following surgery might be explained by a disruption of immuno-inflammatory cascades involving a few crucial molecules which could serve as potential therapeutic targets.
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Nutriomics team, F-75005, Paris, France.
Christine
C
Poitou
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Genomics and Pathophysiology of Cardiovascular Diseases team, F-75013, Paris, France.
Claire
C
Perret
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Genomics and Pathophysiology of Cardiovascular Diseases team, F-75013, Paris, France.
François
F
Mathieu
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Genomics and Pathophysiology of Cardiovascular Diseases team, F-75013, Paris, France.
Vinh
V
Truong
Department of Medicine/Division of Cardiology, University of California Los Angeles, Los Angeles, California 90095, United States of America.
Yuna
Y
Blum
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Genomics and Pathophysiology of Cardiovascular Diseases team, F-75013, Paris, France.
Hervé
H
Durand
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Nutriomics team, F-75005, Paris, France.
Rohia
R
Alili
Sorbonne Universités, University Pierre et Marie Curie (UPMC), Post-Genomic Platform of Pitié-Salpêtrière (P3S), F-75013, Paris, France.
Nadjim
N
Chelghoum
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Nutriomics team, F-75005, Paris, France.
Véronique
V
Pelloux
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Nutriomics team, F-75005, Paris, France.
Judith
J
Aron-Wisnewsky
Assistance Publique-Hôpitaux de Paris, Department of Visceral Surgery, Pitié-Salpêtrière Hospital, F-75013, Paris, France.
Adriana
A
Torcivia
Assistance Publique-Hôpitaux de Paris, Department of General, Digestive and Metabolic Surgery, Ambroise-Paré Hospital, F- 92100, Boulogne-Billancourt, France.
Jean-Luc
JL
Bouillot
Department of Medicine/Division of Cardiology, University of California Los Angeles, Los Angeles, California 90095, United States of America.
Brian W
BW
Parks
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Genomics and Pathophysiology of Cardiovascular Diseases team, F-75013, Paris, France.
Ewa
E
Ninio
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Nutriomics team, F-75005, Paris, France.
Karine
K
Clément
Institute of Cardiometabolism And Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Nutrition Department, F-75013, Paris, France; Sorbonne Universités, University Pierre et Marie Curie (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1166, Genomics and Pathophysiology of Cardiovascular Diseases team, F-75013, Paris, France.
Laurence
L
Tiret
D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism*; D000328:Adult; D000818:Animals; D050110:Bariatric Surgery / Q000009:adverse effects*; D016000:Cluster Analysis; D019295:Computational Biology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007372:Interferons / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
D007372:Interferons