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Transcriptomic profiling of the liver after Roux-en-Y gastric bypass in a humanized murine model of the metabolic syndrome

ABSTRACT: The metabolic syndrome (MetS) is attributed to a number of risk factors related to obesity and its comorbidities such as hypertension, increased blood glucose, hypertriglyceridemia and cardiovascular disease (CAD). Several mouse models have been used trying to understand the metabolic abnormalities occur in obesity and MetS. However, The ApoE*3Leiden.human Cholesteryl Ester Transfer Protein (ApoE3L.CETP) mouse model better describes the physiology and pathophysiology of the MetS upon high fat diet (HFD) feeding. Towards MetS treatment, Roux-en-Y gastric bypass (RYGB) is a surgical bariatric approach that allows to achieve sustained and long-term weight loss and to improve comorbidities of the MetS. The aim of this study was to elucidate whether improvements in lipid and glucose metabolism after RYGB surgery are body weight-dependent or not and to identify transcriptomic signatures related to these phenotypic observations.

ORGANISM(S): Mus musculus

PROVIDER: GSE125946 | GEO | 2019/07/05

REPOSITORIES: GEO

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Project description:INTRODUCTION: Bariatric surgery is known to be the most effective treatment for weight loss in obese patients and for the rapid remission of obesity-related comorbidities. These short-term improvements result from not only limited digestion or absorption but also dynamic changes in metabolism throughout the whole body. However, short-term metabolism studies associated with bariatric surgery in Asian individuals have not been reported.OBJECTIVES: The aim of this study was to investigate the short-term metabolome changes in the serum promoted by laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and to determine the underlying mechanisms that affect obesity-related comorbidities.METHODS: Serum samples were collected from Korean patients who underwent RYGB or SG before and 4 weeks after the surgery. Metabolomic and lipidomic profiling was performed using UPLC-Orbitrap-MS, and data were analyzed using statistical analysis.RESULTS: Metabolites mainly related to amino acids, lipids (fatty acids, glycerophospholipids, sphingolipids, glycerolipids) and bile acids changed after surgery, and these changes were associated with the lowering of risk factors for obesity-related diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and atherosclerosis. Interestingly, the number of significantly altered metabolites related to the lipid metabolism were greater in SG than in RYGB. Furthermore, the metabolites related to amino acid metabolism were significantly changed only after SG, whereas bile acid changed significantly only following RYGB.CONCLUSION: These differences could result from anatomical differences between the two surgeries and could be related to the gut microbiota. This study provides crucial information to expand the knowledge of the common but different molecular mechanisms involved in obesity and obesity-related comorbidities affected by each bariatric procedure.

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Transcriptomic profiling of the liver after Roux-en-Y gastric bypass in a humanized murine model of the metabolic syndrome

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