# Saturated fat exacerbates mitochondrial dysfunction through remodelling of ATP production and inflammation in Barrett’s oesophagus compared to monounsaturated fat, particularly in contrast to oesophageal adenocarcinoma

## TL;DR

Saturated fat worsens mitochondrial issues and inflammation in Barrett’s oesophagus more than monounsaturated fat, potentially increasing the risk of oesophageal cancer.

## Contribution

The study reveals that saturated fat uniquely exacerbates mitochondrial dysfunction and oncogenic signaling in Barrett’s oesophagus compared to monounsaturated fat.

## Key findings

- SFA increases fatty acid metabolism and mitochondrial dysfunction in Barrett’s oesophagus but not in OAC cells.
- SFA reduces mitochondrial ATP production in both Barrett’s oesophagus and OAC cells.
- SFA promotes a more pro-inflammatory and metabolic adverse phenotype compared to MUFA in Barrett’s oesophagus.

## Abstract

Obesity-related oesophageal adenocarcinoma (OAC), arising from Barrett’s oesophagus (BO), incidence rates are rising coincident with high-fat diets. However, adipose tissue phenotype drives metabolic characteristics. Prior feeding studies demonstrated that obesogenic diets enriched in saturated fatty acids (SFA) induce a more adverse metabolic and pro-inflammatory adipose phenotype, compared to monounsaturated fatty acids (MUFA) enriched high-fat diets, despite equal obesity. We hypothesise that different fatty acids may alter the progression of BO to OAC, wherein SFA may be more pathogenic compared to MUFA. Proteomic analysis shows that SFA, not MUFA, increases fatty acid metabolism, oncogenic signalling, and mitochondrial respiratory chain to a greater extent in BO but not in OAC cells. Cellular metabolic analysis validated proteomic findings to show mitochondrial dysfunction in BO but showed an increase in glycolysis in OAC following SFA treatment compared to MUFA. Additionally, it showed a decrease in mitochondrial ATP production following treatment of SFA in BO and OAC cells. Reduction of SFA intake may be beneficial as a supplementary treatment approach to manage and/or prevent OAC progression.