Body weight-dependent and independent improvement in lipid metabolism after Roux-en-Y gastric bypass in ApoE3Leiden.CETP mice

• Published in: International Journal of Obesity Vol. 43; no. 12; pp. 2394 - 2406
• Main Authors: Tarasco, Erika, Boyle, Christina N., Pellegrini, Giovanni, Arnold, Myrtha, Steiner, Regula, Hornemann, Thorsten, Nasias, Dimitris, Kardassis, Dimitris, Whiting, Lynda, Lutz, Thomas A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2019; Nature Publishing Group
• Subjects: 14/63; 38/61; 631/443/319/1642/2037; 631/443/592/75; 64/60; Analysis; Animals; Antilipemic agents; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - genetics; Blood Glucose - metabolism; Body fat; Body weight; Body Weight - physiology; Body weight loss; Ceramide; Cholesterol; Comorbidity; Dextrose; Disease Models, Animal; Eating - physiology; Epidemiology; Ethylenediaminetetraacetic acid; Food availability; Gastric Bypass; Gastrointestinal surgery; Gene expression; Glucose; Glucose metabolism; Glucose tolerance; Health Promotion and Disease Prevention; High density lipoprotein; Histology; Insulin; Internal Medicine; Lipid metabolism; Lipid Metabolism - physiology; Lipids; Liver; Liver - chemistry; Liver - physiology; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - physiopathology; Metabolism; Mice; Mice, Transgenic; Obesity; Public Health; Reduction; Sensitivity analysis; Surgery; Type 2 diabetes; Weight loss; Weight Loss - physiology
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/s41366-019-0408-y

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.