Mitochondrial energy metabolism in a model of undernutrition induced by dexamethasone.
The present investigation was undertaken to evaluate whether mitochondrial energy metabolism is altered in a model of malnutrition induced by dexamethasone (DEX) treatment (1.5 mg/kg per d for 5 d). The gastrocnemius and liver mitochondria were isolated from DEX-treated, pair-fed (PF) and control (CON) rats. Body weight was reduced significantly more in the DEX-treated group (-16%) than in the PF group (-9%). DEX treatment increased liver mass (+59% v. PF, +23% v. CON) and decreased gastrocnemius mass. Moreover, in DEX-treated rats, liver mitochondria had an increased rate of non-phosphorylative O2 consumption with all substrates (approximately +42%). There was no difference in enzymatic complex activities in liver mitochondria between rat groups. Collectively, these results suggest an increased proton leak and/or redox slipping in the liver mitochondria of DEX-treated rats. In addition, DEX decreased the thermodynamic coupling and efficiency of oxidative phosphorylation. We therefore suggest that this increase in the proton leak and/or redox slip in the liver is responsible for the decrease in the thermodynamic efficiency of energy conversion. In contrast, none of the variables of energy metabolism determined in gastrocnemius mitochondria was altered by DEX treatment. Therefore, it appears that DEX specifically affects mitochondrial energy metabolism in the liver.
Dumas
Jean-François
JF
Medecine B, CHU, F-49033 Angers Cedex 01, France.
Simard
Gilles
G
Roussel
Damien
D
Douay
Olivier
O
Foussard
Françoise
F
Malthiery
Yves
Y
Ritz
Patrick
P
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009748:Nutrition Disorders / Q000139:chemically induced / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates / Q000378:metabolism
D005938:Glucocorticoids; D005971:Glutamates; D013386:Succinates; D003907:Dexamethasone; D002950:Citrate (si)-Synthase