ESPEN 2020 Abstract Submission

Topic: Nutrition and cancer

Abstract Submission Identifier: ESPEN20-ABS-1180

HEPATIC AND MUSCULAR MITOCHONDRIAL DYSFUNCTION AND ENERGY METABOLISM DISTURBANCES IN A MURINE COLON WARD CANCER AND CHEMOTHERAPY MODEL.

M. BOUTIERE^*, ¹, G. VIAL ², F. LAMARCHE ¹, H. DUBOUCHAUD ¹, E. FONTAINE ¹, C. MOINARD ¹, C. BREUILLARD ¹

¹LBFA, INSERM U1055, ²HP2, INSERM U1042, Grenoble, France

Rationale: In a previous study we showed that in the presence of cancer and chemotherapy (in a situation of extra hepatic tumor) there was a liver mitochondrial dysfunction. In addition, there is a disruption of energy metabolism during cachexia (1). Our objective was to determine if cancer and/or chemotherapy was responsible of this latter in a cachexia model cancer associated to chemotherapy (2), and there was a possible relationship with an impairment of hepatic and/or muscular mitochondrial function.

Methods: Female Fisher rats (10 weeks-old) were randomized in four groups (n=8/group): a healthy group (Ct); a cancer group (Ca); a chemotherapy group (Ch) and a cancer + chemotherapy group (CC). Cancer was injected subcutaneously, and chemotherapy was administred in two cycles on a week apart, each consisting in one injection of Irinotecan (50 mg/kg) and one of 5-Fluorouracil (50 mg/kg). After the injection of cancer or chemotherapy, rats were housed in metabolic cages for 18 hours. At euthanasia, liver and quadriceps were removed and mitochondria isolated. The following tests were then performed on mitochondria: Wastes (proton leak and/or redox slipping) as described (3), mitochondrial reactive oxygen species (ROS) production, respiration during ATP synthesis and efficiency of ATP synthesis. Liver and muscle mitochondrial density was evaluated by Citrate Synthase Activity (CS). Results were expressed in mean±SEM except for energy balance (MED ± [min;max]), * is significantly different from Ct (<0.05).

Results: In liver and muscle mitochondria, respiration compared to proton-motive force, efficiency of ATP synthesis were not affected by cancer and/or chemotherapy. Energy balance, respiration (nmol O₂/min/activity of CS) and ROS production (nmol H₂O₂/min/activity of CS) in muscle and hepatic mitochondria are summarized below:

Groups	Energy balance (kcal/day)	Respiration in muscle	Respiration in liver	ROS Production in muscle	ROS production in liver
Ct	-1.8 [-9.7;14.3]	0.19±0.01	0.60±0.15	1.4±0.08	1.8±0.10
Ca	-4.1 [-15.6;0.08]	0.25±0.01*	0.30±0.10*	1.6±0.10	1.3±0.10*
Ch	-28.9 [-31.2;23.7]*	0.21±0.01	0.41±0.11	1.6±0.10	1.2±0.08*
CC	-23.8 [-34.4;-15.2]*	0.23±0.02*	0.33±0.07*	1.7±0.05*	1.2±0.04*

Conclusion: Our results suggest that i) our model is well characterized by an energy metabolism disturbances, ii) mainly related to chemotherapy, and iii) possibly related to liver and muscle mitochondrial dysfunction.

References: 1. De Vos-Geelen et al., Curr Opin Clin Nutr Metab Care,. 2014

2. Xue et al., Br J Nutr., 2009

3. Nicholls et al., Methods Mol Biol., 2012

Disclosure of Interest: None Declared

Keywords: Metabolism, Mitochondria