title: Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity.
abstract: OBJECTIVE
  Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, hepatocyte ballooning with fibrosis in severe cases, and high prevalence in obesity. We aimed at defining NASH signature in morbid obesity by mass spectrometry-based lipidomic analysis.
  
  
  METHODS
  We analyzed systemic blood before and 12 months after bariatric surgery, along with portal blood and adipose tissue lipid efflux collected from obese women at the time of surgery (9 structural classes, 150 species).
  
  
  RESULTS
  Increased concentrations of several glycerophosphocholines (PC), glycerophosphoethanolamines (PE), glycerophosphoinositols (PI), glycerophosphoglycerols (PG), lyso-glycerophosphocholines (LPC), and ceramides (Cer) were detected in systemic circulation of NASH subjects. Post-surgery weight loss (12 months) improved the levels of liver enzymes, as well as several lipids, but most PG and Cer species remained elevated. Analysis of lipids from hepatic portal system at the time of surgery revealed limited lipid alterations compared to systemic circulation, but PG and PE classes were found significantly increased in NASH subjects. We evaluated the contribution of visceral adipose tissue to lipid alterations in portal circulation by measuring adipose tissue lipid efflux ex vivo, and observed only minor alterations in NASH subjects. Interestingly, integration of clinical and lipidomic data (portal and systemic) led us to define a NASH signature in which lipids and clinical parameters are equal contributors.
  
  
  CONCLUSIONS
  Circulatory (portal and systemic) phospholipid profiling and clinical data defines NASH signature in morbid obesity. We report weak contribution of visceral adipose tissue to NASH-related portal lipid alterations, suggesting possible contribution from other organs draining into hepatic portal system.
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UMR_S 1166 I, ICAN, Nutriomics Team, F-75005 Paris, France; INSERM, UMR_S U1166, Nutriomics Team, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France.
authors.forename: Kavya
authors.initials: K
authors.lastname: Anjani
authors.affiliation: Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lhomme
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UMR_S 1166 I, ICAN, Nutriomics Team, F-75005 Paris, France; INSERM, UMR_S U1166, Nutriomics Team, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Sokolovska
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UMR_S 1166 I, ICAN, Nutriomics Team, F-75005 Paris, France; INSERM, UMR_S U1166, Nutriomics Team, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Poitou
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UMR_S 1166 I, ICAN, Nutriomics Team, F-75005 Paris, France; INSERM, UMR_S U1166, Nutriomics Team, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Aron-Wisnewsky
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Ambroise Pare Hospital, Surgery Department, Boulogne-Billancourt, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bouillot
authors.affiliation: Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France; INSERM, UMR_S U1166, Dyslipidemia, Inflammation and Atherosclerosis Team, F-75013 Paris, France; Sorbonne Universités, UPMC Université Paris 06, UMR_S 1166 I, ICAN, Dyslipidemia. Inflammation and Atherosclerosis Team, F-75005 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Beaujon Hospital, Pathology Department, Clichy, France; Centre de Recherche Bichat-Beaujon, INSERM U773, University Paris-Diderot, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.affiliation: Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France; INSERM, UMR_S U1166, Dyslipidemia, Inflammation and Atherosclerosis Team, F-75013 Paris, France; Sorbonne Universités, UPMC Université Paris 06, UMR_S 1166 I, ICAN, Dyslipidemia. Inflammation and Atherosclerosis Team, F-75005 Paris, France.
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UMR_S 1166 I, ICAN, Nutriomics Team, F-75005 Paris, France; INSERM, UMR_S U1166, Nutriomics Team, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Clement
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UMR_S 1166 I, ICAN, Nutriomics Team, F-75005 Paris, France; INSERM, UMR_S U1166, Nutriomics Team, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France. Electronic address: isabelle.dugail@inserm.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dugail
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UMR_S 1166 I, ICAN, Nutriomics Team, F-75005 Paris, France; INSERM, UMR_S U1166, Nutriomics Team, F-75013 Paris, France; Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France. Electronic address: joan.tordjman@crc.jussieu.fr.
authors.forename: Joan
authors.initials: J
authors.lastname: Tordjman
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000328:Adult; D050110:Bariatric Surgery / Q000009:adverse effects / Q000379:methods; D002518:Ceramides / Q000097:blood / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005602:France; D020404:Glycerophospholipids / Q000097:blood / Q000145:classification / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000209:etiology / Q000473:pathology; D009767:Obesity, Morbid / Q000097:blood / Q000150:complications / Q000601:surgery; D011168:Portal System / Q000378:metabolism; D011183:Postoperative Complications / Q000097:blood*; D011184:Postoperative Period
chemical_list: D002518:Ceramides; D020404:Glycerophospholipids
keywords: Bariatric surgery; Glycerophosphatidylethanolamines; Glycerophosphatidylglycerols; Lipidomics; Visceral adipose tissue