Type

Journal Article

Authors

Lorraine Brennan
Naoimh J O'Farrell
Richard Porter
Ann-Marie Mongan
Graham Pidgeon
Eibhlin Carr
Jacintha O'Sullivan
Ruth Connaughton
John Reynolds
Joanne Lysaght
and 1 others

Subjects

Biochemistry

Topics
obesity adipose tissue genetics cell line tumor thyroid hormones male deoxyglucose antimetabolites mitochondrial dysfunction mitochondrial mass middle aged mitochondria intra abdominal fat aged pharmacology physiology diagnostic imaging cell lines membrane proteins obesity abdominal thyroid hormone binding proteins complications glycolysis genes mitochondrial bioenergetics carrier proteins culture media conditioned metabolome body mass index physiopathology membrane potential mitochondrial adenocarcinoma esophageal neoplasms obesity mitochondrial dysfunction bioenergetics metabolomics energy metabolism computed tomography adenosine triphosphate reactive oxygen species humans metabolism radiography gene expression female metabolomics drug effects

Excess visceral adiposity induces alterations in mitochondrial function and energy metabolism in esophageal adenocarcinoma. (2014)

Abstract Background Visceral obesity has a strong association with both the incidence and mortality of esophageal adenocarcinoma (EAC). Alterations in mitochondrial function and energy metabolism is an emerging hallmark of cancer, however, the potential role that obesity plays in driving these alterations in EAC is currently unknown. Methods Adipose conditioned media (ACM) was prepared from visceral adipose tissue taken from computed tomography-determined viscerally-obese and non-obese EAC patients. Mitochondrial function in EAC cell lines was assessed using fluorescent probes, mitochondrial gene expression was assessed using qPCR-based gene arrays and intracellular ATP levels were determined using a luminescence-based kit. Glycolysis and oxidative phosphophorylation was measured using Seahorse XF technology and metabolomic analysis was performed using 1H NMR. Expression of metabolic markers was assessed in EAC tumor biopsies by qPCR. Results ACM from obese EAC patients significantly increased mitochondrial mass and mitochondrial membrane potential in EAC cells, which was significantly associated with visceral fat area, and was coupled with a significant decrease in reactive oxygen species. This mitochondrial dysfunction was accompanied by altered expression of 19 mitochondrial-associated genes and significantly reduced intracellular ATP levels. ACM from obese EAC patients induced a metabolic shift to glycolysis in EAC cells, which was coupled with significantly increased sensitivity to the glycolytic inhibitor 2-deoxyglucose. Metabolomic profiling demonstrated an altered glycolysis and amino acid-related signature in ACM from obese patients. In EAC tumors, expression of the glycolytic marker PKM2 was significantly positively associated with obesity. Conclusion This study demonstrates for the first time that ACM from viscerally-obese EAC patients elicits an altered metabolic profile and can drive mitochondrial dysfunction and altered energy metabolism in EAC cells in vitro. In vivo, in EAC patient tumors, expression of the glycolytic enzyme PKM2 is positively associated with obesity.
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Full list of authors on original publication

Lorraine Brennan, Naoimh J O'Farrell, Richard Porter, Ann-Marie Mongan, Graham Pidgeon, Eibhlin Carr, Jacintha O'Sullivan, Ruth Connaughton, John Reynolds, Joanne Lysaght and 1 others

Experts in our system

1
Lorraine Brennan
University College Dublin
Total Publications: 166
 
2
N J O'Farrell
Trinity College Dublin
Total Publications: 14
 
3
Richard K Porter
Trinity College Dublin
Total Publications: 52
 
4
Ann-Marie Mongan
Trinity College Dublin
Total Publications: 6
 
5
Graham Pidgeon
Trinity College Dublin
Total Publications: 38
 
6
Jacintha O'Sullivan
Trinity College Dublin
Total Publications: 74
 
7
Ruth M Connaughton
University College Dublin
Total Publications: 6
 
8
J V Reynolds
Trinity College Dublin
Total Publications: 206
 
9
Joanne Lysaght
Trinity College Dublin
Total Publications: 39