Adhesion phenotype manifests an altered metabolic profile favoring glycolysis

Capsule:
Adhesion fibroblasts manifested an altered metabolic profile as compared with normal peritoneal fibroblasts, which favors the glycolytic pathway, and is further altered by hypoxia.

Authors:
Nicole M. Fletcher, Ph.D., Awoniyi O. Awonuga, M.D., Mohammed S. Abusamaan, M.D., Mohammed G. Saed, B.A., Michael P. Diamond, M.D., Ghassan M. Saed, Ph.D.

Volume 105, Issue 6, Pages 1628-1637

Abstract:

Objective:
To determine whether metabolic markers are differentially expressed in normal and adhesion fibroblasts with and without hypoxia exposure.

Design:
Prospective experimental study.

Setting:
University research laboratory.

Patient(s):
Fibroblasts established from normal peritoneum and adhesion tissues from the same patients.

Intervention(s):
In vitro experiments on normal peritoneal and adhesion fibroblasts under normal and hypoxic (2% O2) conditions.

Main Outcome Measure(s):
Expression of metabolic markers, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), glucose transporter 1 (GLUT1), hypoxia inducible factor (HIF)-1α, hexokinase 2 (HK2), lactose dehydrogenase A (LDHA), and pyruvate dehydrogenase alpha 1 (PDHA1) were measured using real-time reverse transcription polymerase chain reaction; adenosine triphosphate (ATP), HIF-1α, and lactate levels were assessed with ELISAs.

Result(s):
Baseline mRNA levels of GAPDH and HIF-1α were increased, while GLUT1 and PDHA1 were decreased in adhesion as compared with in normal peritoneal fibroblasts. There was no change in baseline levels of HK2 or LDHA between the cell lines. Hypoxia increased protein levels of HIF-1α and mRNA levels of GAPDH, GLUT1, and HK2 and decreased levels of PDHA1 in both cell lines. Hypoxia increased LDHA mRNA levels in normal peritoneal fibroblasts. Baseline levels of lactate and ATP were lower in adhesion as compared with in normal peritoneal fibroblasts. In response to hypoxia, there was an increase in lactate in both cell lines and a decrease in ATP in normal fibroblasts.

Conclusion(s):
Adhesion fibroblasts manifested an altered metabolic profile, which favors the glycolytic pathway, and is further altered by hypoxia. Targeting these specific metabolic markers during surgery can be an important therapeutic intervention minimizing the development of postoperative adhesions.

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