Erika Tarasco1,2, Christina N Boyle1, Giovanni Pellegrini3,4, Myrtha Arnold5, Regula Steiner6, Thorsten Hornemann2,6, Dimitris Nasias7, Dimitris Kardassis7, Lynda Whiting8, Thomas A Lutz9,10. 1. Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich, Zurich, Switzerland. 2. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. 3. Laboratory for Animal Model Pathology (LAMP), Institute of Veterinary Pathology, Vetsuisse Faculty University of Zurich, Zurich, Switzerland. 4. Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden. 5. Physiology and Behaviour Laboratory, ETH Zurich, Schwerzenbach, Switzerland. 6. Institute of Clinical Chemistry, University and University Hospital of Zurich, Zurich, Switzerland. 7. Department of Basic Medical Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Crete, Greece. 8. Institute of "Drug and Discovery Biology", University of Monash, VIC, Australia. 9. Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich, Zurich, Switzerland. tomlutz@vetphys.uzh.ch. 10. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. tomlutz@vetphys.uzh.ch.
Abstract
BACKGROUND/ OBJECTIVES: The incidence of obesity and metabolic syndrome (MetS) has rapidly increased worldwide. Roux-en-Y gastric bypass (RYGB) achieves long-term weight loss and improves MetS-associated comorbidities. Using a mouse model with a humanized lipoprotein metabolism, we elucidated whether improvements in lipid and glucose metabolism after RYGB surgery are body weight loss-dependent or not. SUBJECTS/ METHODS: Male ApoE*3Leiden.CETP (ApoE3L.CETP) mice fed Western type diet for 6 weeks underwent RYGB or Sham surgery. Sham groups were either fed ad libitum or were body weight-matched (BWm) to the RYGB mice to discriminate surgical effects from body weight loss-associated effects. Before and after surgery, plasma was collected to assess the metabolic profile, and glucose tolerance and insulin sensitivity were tested. Twenty days after surgery, mice were sacrificed, and liver was collected to assess metabolic, histological and global gene expression changes after surgery. RESULTS: RYGB induced a marked reduction in body weight, which was also achieved by severe food restriction in BWm mice, and total fat mass compared to Sham ad libitum mice (Sham AL). Total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and ceramide were strongly reduced 20 days after surgery in RYGB compared to BWm mice. Glucose tolerance and insulin sensitivity improved 13 days after surgery similarly in RYGB and BWm mice. Liver histology confirmed lipid reduction in RYGB and BWm mice while the transcriptomics data indicated altered genes expression in lipid metabolism. CONCLUSIONS: RYGB surgery improves glucose metabolism and greatly ameliorates lipid metabolism in part in a body weight-dependent manner. Given that ApoE3L.CETP mice were extensively studied to describe the MetS, and given that RYGB improved ceramide after surgery, our data confirmed the usefulness of ApoE3L.CETP mice after RYGB in deciphering the metabolic improvements to treat the MetS.
BACKGROUND/ OBJECTIVES: The incidence of obesity and metabolic syndrome (MetS) has rapidly increased worldwide. Roux-en-Y gastric bypass (RYGB) achieves long-term weight loss and improves MetS-associated comorbidities. Using a mouse model with a humanized lipoprotein metabolism, we elucidated whether improvements in lipid and glucose metabolism after RYGB surgery are body weight loss-dependent or not. SUBJECTS/ METHODS: Male ApoE*3Leiden.CETP (ApoE3L.CETP) mice fed Western type diet for 6 weeks underwent RYGB or Sham surgery. Sham groups were either fed ad libitum or were body weight-matched (BWm) to the RYGB mice to discriminate surgical effects from body weight loss-associated effects. Before and after surgery, plasma was collected to assess the metabolic profile, and glucose tolerance and insulin sensitivity were tested. Twenty days after surgery, mice were sacrificed, and liver was collected to assess metabolic, histological and global gene expression changes after surgery. RESULTS: RYGB induced a marked reduction in body weight, which was also achieved by severe food restriction in BWm mice, and total fat mass compared to Sham ad libitum mice (Sham AL). Total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and ceramide were strongly reduced 20 days after surgery in RYGB compared to BWm mice. Glucose tolerance and insulin sensitivity improved 13 days after surgery similarly in RYGB and BWm mice. Liver histology confirmed lipid reduction in RYGB and BWm mice while the transcriptomics data indicated altered genes expression in lipid metabolism. CONCLUSIONS: RYGB surgery improves glucose metabolism and greatly ameliorates lipid metabolism in part in a body weight-dependent manner. Given that ApoE3L.CETP mice were extensively studied to describe the MetS, and given that RYGB improved ceramide after surgery, our data confirmed the usefulness of ApoE3L.CETP mice after RYGB in deciphering the metabolic improvements to treat the MetS.
Authors: Paul Poirier; Marc-André Cornier; Theodore Mazzone; Sasha Stiles; Susan Cummings; Samuel Klein; Peter A McCullough; Christine Ren Fielding; Barry A Franklin Journal: Circulation Date: 2011-03-14 Impact factor: 29.690
Authors: Harold E Bays; Peter P Toth; Penny M Kris-Etherton; Nicola Abate; Louis J Aronne; W Virgil Brown; J Michael Gonzalez-Campoy; Steven R Jones; Rekha Kumar; Ralph La Forge; Varman T Samuel Journal: J Clin Lipidol Date: 2013-05-31 Impact factor: 4.766
Authors: Elizabeth K Speliotes; Cristen J Willer; Sonja I Berndt; Keri L Monda; Gudmar Thorleifsson; Anne U Jackson; Hana Lango Allen; Cecilia M Lindgren; Jian'an Luan; Reedik Mägi; Joshua C Randall; Sailaja Vedantam; Thomas W Winkler; Lu Qi; Tsegaselassie Workalemahu; Iris M Heid; Valgerdur Steinthorsdottir; Heather M Stringham; Michael N Weedon; Eleanor Wheeler; Andrew R Wood; Teresa Ferreira; Robert J Weyant; Ayellet V Segrè; Karol Estrada; Liming Liang; James Nemesh; Ju-Hyun Park; Stefan Gustafsson; Tuomas O Kilpeläinen; Jian Yang; Nabila Bouatia-Naji; Tõnu Esko; Mary F Feitosa; Zoltán Kutalik; Massimo Mangino; Soumya Raychaudhuri; Andre Scherag; Albert Vernon Smith; Ryan Welch; Jing Hua Zhao; Katja K Aben; Devin M Absher; Najaf Amin; Anna L Dixon; Eva Fisher; Nicole L Glazer; Michael E Goddard; Nancy L Heard-Costa; Volker Hoesel; Jouke-Jan Hottenga; Asa Johansson; Toby Johnson; Shamika Ketkar; Claudia Lamina; Shengxu Li; Miriam F Moffatt; Richard H Myers; Narisu Narisu; John R B Perry; Marjolein J Peters; Michael Preuss; Samuli Ripatti; Fernando Rivadeneira; Camilla Sandholt; Laura J Scott; Nicholas J Timpson; Jonathan P Tyrer; Sophie van Wingerden; Richard M Watanabe; Charles C White; Fredrik Wiklund; Christina Barlassina; Daniel I Chasman; Matthew N Cooper; John-Olov Jansson; Robert W Lawrence; Niina Pellikka; Inga Prokopenko; Jianxin Shi; Elisabeth Thiering; Helene Alavere; Maria T S Alibrandi; Peter Almgren; Alice M Arnold; Thor Aspelund; Larry D Atwood; Beverley Balkau; Anthony J Balmforth; Amanda J Bennett; Yoav Ben-Shlomo; Richard N Bergman; Sven Bergmann; Heike Biebermann; Alexandra I F Blakemore; Tanja Boes; Lori L Bonnycastle; Stefan R Bornstein; Morris J Brown; Thomas A Buchanan; Fabio Busonero; Harry Campbell; Francesco P Cappuccio; Christine Cavalcanti-Proença; Yii-Der Ida Chen; Chih-Mei Chen; Peter S Chines; Robert Clarke; Lachlan Coin; John Connell; Ian N M Day; Martin den Heijer; Jubao Duan; Shah Ebrahim; Paul Elliott; Roberto Elosua; Gudny Eiriksdottir; Michael R Erdos; Johan G Eriksson; Maurizio F Facheris; Stephan B Felix; Pamela Fischer-Posovszky; Aaron R Folsom; Nele Friedrich; Nelson B Freimer; Mao Fu; Stefan Gaget; Pablo V Gejman; Eco J C Geus; Christian Gieger; Anette P Gjesing; Anuj Goel; Philippe Goyette; Harald Grallert; Jürgen Grässler; Danielle M Greenawalt; Christopher J Groves; Vilmundur Gudnason; Candace Guiducci; Anna-Liisa Hartikainen; Neelam Hassanali; Alistair S Hall; Aki S Havulinna; Caroline Hayward; Andrew C Heath; Christian Hengstenberg; Andrew A Hicks; Anke Hinney; Albert Hofman; Georg Homuth; Jennie Hui; Wilmar Igl; Carlos Iribarren; Bo Isomaa; Kevin B Jacobs; Ivonne Jarick; Elizabeth Jewell; Ulrich John; Torben Jørgensen; Pekka Jousilahti; Antti Jula; Marika Kaakinen; Eero Kajantie; Lee M Kaplan; Sekar Kathiresan; Johannes Kettunen; Leena Kinnunen; Joshua W Knowles; Ivana Kolcic; Inke R König; Seppo Koskinen; Peter Kovacs; Johanna Kuusisto; Peter Kraft; Kirsti Kvaløy; Jaana Laitinen; Olivier Lantieri; Chiara Lanzani; Lenore J Launer; Cecile Lecoeur; Terho Lehtimäki; Guillaume Lettre; Jianjun Liu; Marja-Liisa Lokki; Mattias Lorentzon; Robert N Luben; Barbara Ludwig; Paolo Manunta; Diana Marek; Michel Marre; Nicholas G Martin; Wendy L McArdle; Anne McCarthy; Barbara McKnight; Thomas Meitinger; Olle Melander; David Meyre; Kristian Midthjell; Grant W Montgomery; Mario A Morken; Andrew P Morris; Rosanda Mulic; Julius S Ngwa; Mari Nelis; Matt J Neville; Dale R Nyholt; Christopher J O'Donnell; Stephen O'Rahilly; Ken K Ong; Ben Oostra; Guillaume Paré; Alex N Parker; Markus Perola; Irene Pichler; Kirsi H Pietiläinen; Carl G P Platou; Ozren Polasek; Anneli Pouta; Suzanne Rafelt; Olli Raitakari; Nigel W Rayner; Martin Ridderstråle; Winfried Rief; Aimo Ruokonen; Neil R Robertson; Peter Rzehak; Veikko Salomaa; Alan R Sanders; Manjinder S Sandhu; Serena Sanna; Jouko Saramies; Markku J Savolainen; Susann Scherag; Sabine Schipf; Stefan Schreiber; Heribert Schunkert; Kaisa Silander; Juha Sinisalo; David S Siscovick; Jan H Smit; Nicole Soranzo; Ulla Sovio; Jonathan Stephens; Ida Surakka; Amy J Swift; Mari-Liis Tammesoo; Jean-Claude Tardif; Maris Teder-Laving; Tanya M Teslovich; John R Thompson; Brian Thomson; Anke Tönjes; Tiinamaija Tuomi; Joyce B J van Meurs; Gert-Jan van Ommen; Vincent Vatin; Jorma Viikari; Sophie Visvikis-Siest; Veronique Vitart; Carla I G Vogel; Benjamin F Voight; Lindsay L Waite; Henri Wallaschofski; G Bragi Walters; Elisabeth Widen; Susanna Wiegand; Sarah H Wild; Gonneke Willemsen; Daniel R Witte; Jacqueline C Witteman; Jianfeng Xu; Qunyuan Zhang; Lina Zgaga; Andreas Ziegler; Paavo Zitting; John P Beilby; I Sadaf Farooqi; Johannes Hebebrand; Heikki V Huikuri; Alan L James; Mika Kähönen; Douglas F Levinson; Fabio Macciardi; Markku S Nieminen; Claes Ohlsson; Lyle J Palmer; Paul M Ridker; Michael Stumvoll; Jacques S Beckmann; Heiner Boeing; Eric Boerwinkle; Dorret I Boomsma; Mark J Caulfield; Stephen J Chanock; Francis S Collins; L Adrienne Cupples; George Davey Smith; Jeanette Erdmann; Philippe Froguel; Henrik Grönberg; Ulf Gyllensten; Per Hall; Torben Hansen; Tamara B Harris; Andrew T Hattersley; Richard B Hayes; Joachim Heinrich; Frank B Hu; Kristian Hveem; Thomas Illig; Marjo-Riitta Jarvelin; Jaakko Kaprio; Fredrik Karpe; Kay-Tee Khaw; Lambertus A Kiemeney; Heiko Krude; Markku Laakso; Debbie A Lawlor; Andres Metspalu; Patricia B Munroe; Willem H Ouwehand; Oluf Pedersen; Brenda W Penninx; Annette Peters; Peter P Pramstaller; Thomas Quertermous; Thomas Reinehr; Aila Rissanen; Igor Rudan; Nilesh J Samani; Peter E H Schwarz; Alan R Shuldiner; Timothy D Spector; Jaakko Tuomilehto; Manuela Uda; André Uitterlinden; Timo T Valle; Martin Wabitsch; Gérard Waeber; Nicholas J Wareham; Hugh Watkins; James F Wilson; Alan F Wright; M Carola Zillikens; Nilanjan Chatterjee; Steven A McCarroll; Shaun Purcell; Eric E Schadt; Peter M Visscher; Themistocles L Assimes; Ingrid B Borecki; Panos Deloukas; Caroline S Fox; Leif C Groop; Talin Haritunians; David J Hunter; Robert C Kaplan; Karen L Mohlke; Jeffrey R O'Connell; Leena Peltonen; David Schlessinger; David P Strachan; Cornelia M van Duijn; H-Erich Wichmann; Timothy M Frayling; Unnur Thorsteinsdottir; Gonçalo R Abecasis; Inês Barroso; Michael Boehnke; Kari Stefansson; Kari E North; Mark I McCarthy; Joel N Hirschhorn; Erik Ingelsson; Ruth J F Loos Journal: Nat Genet Date: 2010-10-10 Impact factor: 38.330