Analysis of Roux-en-Y Gastric Bypass and High-Fat Feeding Reveals Hepatic Transcriptome Reprogramming: Ironing out...

Area of Science:

• * Molecular biology
• * Metabolic research
• * Bariatric surgery outcomes

Background:

• * Roux-en-Y gastric bypass (RYGB) surgery is effective for treating obesity-related metabolic disorders.
• * Post-operative diet composition significantly influences the success of RYGB.
• * Hepatic transcriptional changes in response to RYGB and diet require further investigation.

Purpose of the Study:

• * To investigate how RYGB and a high-fat diet (HFD) differentially regulate hepatic transcriptional programs.
• * To identify specific gene expression patterns associated with RYGB, HFD, and their interaction.
• * To understand the impact of diet on RYGB-induced metabolic improvements at the molecular level.

Main Methods:

• * RNA sequencing (RNA-seq) was performed on liver tissues from diet-induced obese mice 8 weeks after RYGB or sham surgery.
• * Mice were maintained on either a standard chow diet or an HFD.
• * Differential gene expression analysis (DESeq2) and pathway enrichment analysis (STRING) were employed.

Main Results:

• * RYGB induced significant changes in hepatic gene expression, including pathways related to extracellular remodeling and reduced mitochondrial activity.
• * A subset of RYGB-induced genes (119) counteracted obesity-associated transcriptional patterns, termed 'Reversal' genes.
• * HFD significantly altered gene expression, emphasizing stress responses and translational repression, with 426 RYGB-specific HFD-induced genes indicating persistent inflammation and iron dysregulation.

Conclusions:

• * RYGB induces substantial hepatic transcriptomic alterations that mitigate obesity-driven metabolic dysfunction, including iron metabolism pathways.
• * A high-fat diet can partially negate the beneficial effects of RYGB, promoting hepatic inflammation and metabolic stress.
• * Optimizing post-operative nutrition, particularly iron intake, is crucial for maximizing RYGB efficacy and ensuring long-term liver health.