Kavya Anjani1, Marie Lhomme2, Nataliya Sokolovska1, Christine Poitou1, Judith Aron-Wisnewsky1, Jean-Luc Bouillot3, Philippe Lesnik4, Pierre Bedossa5, Anatol Kontush4, Karine Clement1, Isabelle Dugail6, Joan Tordjman7. 1. 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. 2. Institute of Cardiometabolism and Nutrition, ICAN, AP-HP, Pitié-Salpêtrière Hospital, F-75013 Paris, France. 3. Assistance Publique-Hôpitaux de Paris, Ambroise Pare Hospital, Surgery Department, Boulogne-Billancourt, France. 4. 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. 5. Assistance Publique-Hôpitaux de Paris, Beaujon Hospital, Pathology Department, Clichy, France; Centre de Recherche Bichat-Beaujon, INSERM U773, University Paris-Diderot, Paris, France. 6. 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. 7. 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.
Abstract
BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: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 obesewomen 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: B D Kayser; M Lhomme; M C Dao; F Ichou; J-L Bouillot; E Prifti; A Kontush; J-M Chevallier; J Aron-Wisnewsky; I Dugail; K Clément Journal: Int J Obes (Lond) Date: 2017-03-10 Impact factor: 5.095
Authors: Alexandra Feldman; Sebastian K Eder; Thomas K Felder; Lyudmyla Kedenko; Bernhard Paulweber; Andreas Stadlmayr; Ursula Huber-Schönauer; David Niederseer; Felix Stickel; Simon Auer; Elisabeth Haschke-Becher; Wolfgang Patsch; Christian Datz; Elmar Aigner Journal: Am J Gastroenterol Date: 2016-08-16 Impact factor: 10.864
Authors: Bruno Ramos-Molina; Daniel Castellano-Castillo; Oscar Pastor; Luis Ocaña-Wilhelmi; Diego Fernández-García; Manuel Romero-Gómez; Fernando Cardona; Francisco J Tinahones Journal: Obes Surg Date: 2019-03 Impact factor: 4.129
Authors: Kang-Yu Peng; Matthew J Watt; Sander Rensen; Jan Willem Greve; Kevin Huynh; Kaushala S Jayawardana; Peter J Meikle; Ruth C R Meex Journal: J Lipid Res Date: 2018-07-24 Impact factor: 5.922