Dataset Information

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

ABSTRACT: Obesity-related oesophageal adenocarcinoma (OAC), arising from Barret’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. 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Esophagus Adenocarcinoma,Barrett's Esophagus,Colon Cancer

SUBMITTER: Kieran Wynne

LAB HEAD: Professor Helen Roche

PROVIDER: PXD055313 | Pride | 2025-06-16

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	211218kw_KMitchelson_H10_S3-B7_1_2673.d.zip	Other
	211218kw_KMitchelson_H10_S3-B8_1_2674.d.zip	Other
	211218kw_KMitchelson_H11_S3-B10_1_2676.d.zip	Other
	211218kw_KMitchelson_H11_S3-B9_1_2675.d.zip	Other
	211218kw_KMitchelson_H12_S3-B11_1_2677.d.zip	Other

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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.

Mitchelson Kathleen A J KAJ O'Connell Fiona F Wynne Kieran K Matallanas David D O'Sullivan Jacintha J Roche Helen M HM

Neoplasia (New York, N.Y.) 20250516

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 ...[more]

PMID: 40381373

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Project description:High-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the effects of high protein intake on the development of fat deposition and partitioning in response to high-fat and/or HS feeding. A total of thirty adult male Wistar rats were assigned to one of the six dietary regimens with low and high protein, sucrose and fat contents for 5 weeks. Body weight (BW) and food intake were measured weekly. Oral glucose tolerance tests and meal tolerance tests were performed after 4th and 5th weeks of the regimen, respectively. At the end of the study, the rats were killed 2 h after ingestion of a calibrated meal. Blood, tissues and organs were collected for analysis of circulating metabolites and hormones, body composition and mRNA expression in the liver and adipose tissues. No changes were observed in cumulative energy intake and BW gain after 5 weeks of dietary treatment. However, high-protein diets reduced by 20 % the adiposity gain induced by HS and high-sucrose high-fat (HS-HF) diets. Gene expression and transcriptomic analysis suggested that high protein intake reduced liver capacity for lipogenesis by reducing mRNA expressions of fatty acid synthase (fasn), acetyl-CoA carboxylase a and b (Acaca and Acacb) and sterol regulatory element binding transcription factor 1c (Srebf-1c). Moreover, ketogenesis, as indicated by plasma β-hydroxybutyrate levels, was higher in HS-HF-fed mice that were also fed high protein levels. Taken together, these results suggest that high-protein diets may reduce adiposity by inhibiting lipogenesis and stimulating ketogenesis in the liver. Adult male Wistar rats were fed diets with varying amounts of protein, carbohydrates and fat for 5 weeks. At the end of the experiment, rats were killed and tanscriptome analysis was performed on pooled liver samples.