Influence of intensity of food restriction on skeletal muscle mitochondrial energy metabolism in rats.
Variable durations of food restriction (FR; lasting weeks to years) and variable FR intensities are applied to animals in life span-prolonging studies. A reduction in mitochondrial proton leak is suggested as a putative mechanism linking such diet interventions and aging retardation. Early mechanisms of mitochondrial metabolic adaptation induced by FR remain unclear. We investigated the influence of different degrees of FR over 3 days on mitochondrial proton leak and mitochondrial energy metabolism in rat hindlimb skeletal muscle. Animals underwent 25, 50, and 75% and total FR compared with control rats. Proton leak kinetics and mitochondrial functions were investigated in two mitochondrial subpopulations, intermyofibrillar (IMF) and subsarcolemmal (SSM) mitochondria. Regardless of the degree of restriction, skeletal muscle mass was not affected by 3 days of FR. Mitochondrial basal proton conductance was significantly decreased in 50% restricted rats in both mitochondrial subpopulations (46 and 40% for IMF and SSM, respectively) but was unaffected in other groups compared with controls. State 3 and uncoupled state 3 respiration rates were decreased in SSM mitochondria only for 50% restricted rats when pyruvate + malate was used as substrate (-34.5 and -38.9% compared with controls, P < 0.05). IMF mitochondria respiratory rates remained unchanged. Three days of FR, particularly at 50% FR, were sufficient to lower mitochondria energetic metabolism in both mitochondrial populations. Our study highlights an early step in mitochondrial adaptation to FR and the influence of the severity of restriction on this adaptation. This step may be involved in an aging-retardation process.
Johnson
Gyasi
G
Institut National de la Santé et de la Recherche Médicale, Unité 694, Université d'Angers, F-49033 Angers Cedex 01, France.
Roussel
Damien
D
Dumas
Jean-François
JF
Douay
Olivier
O
Malthièry
Yves
Y
Simard
Gilles
G
Ritz
Patrick
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D004032:Diet; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D008293:Malates / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000378:metabolism*; D009929:Organ Size; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D010172:Palmitoylcarnitine / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D008293:Malates; D010172:Palmitoylcarnitine; C030298:malic acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D010100:Oxygen