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

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. For this purpose, 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 group (Sham AL) or were body weight-matched (BWm) to the RYGB mice, in order to identify surgical effects from body weight loss associated effects. The metabolic profile of mice was thoroughly assessed before and after surgery. Mice were sacrificed 20 days after surgery and the livers were collected to assess metabolic, histological and global gene expression changes after surgery. RNA from the three different cohorts of mice (Rygb group, 6 replicates/ Sham AL group, 5 replicates/ BWm group, 4 replicates) was labeled and hybridized to GeneChip™ Mouse Gene 2.0 ST Affymetrix expression arrays. The total of 15 arrays was analyzed to the Affymetrix Expression Console Software Version 1.4.1.46 by applying the robust multi-array average (RMA) algorithm. To determine the differentially expressed genes in the Affymetrix® Transcriptome Analysis Console (TAC) Software (Version 3.1.0.5), we applied the comparisons of the Rygb versus the Sham AL group and the Rygb versus BWm group under specific p-value and fold change thresholds (One Way Analysis of Variance: p-value <0.05 and absolute fold change ≥1.5).