Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats.
The effect of treatment with acetyl-L-carnitine on hepatic mitochondrial respiration and biosynthetic function in perfused liver from young (90 days) and old (22-24 months) rats was studied. Rats were given a 1.5% (w/v) solution of acetyl-L-carnitine in their drinking water for 1 month and oxygen consumption together with the rate of gluconeogenesis, urea synthesis, and ketogenesis with and without added substrates were measured in perfused liver. Mitochondrial oxygen consumption was also assessed in liver homogenate and isolated mitochondria to determine the maximal capacity for oxidative phosphorylation. Acetyl-L-carnitine treatment almost completely restored the age-dependent decline in oxygen consumption, gluconeogenesis, urea synthesis, and ketogenesis found in perfused liver of old rats to the levels found in young rats. In addition, acetyl-L-carnitine treatment increased oxygen consumption and biosynthetic function in perfused liver from young rats. After acetyl-L-carnitine treatment, we found detectable 3-oxoacyl-CoA-transferase activity associated with a consumption of ketone bodies in young and old rats. Finally, oxygen consumption measured in homogenate and isolated mitochondria did not change with age and acetyl-L-carnitine treatment. Our results show that in perfused liver, acetyl-L-carnitine treatment slows the age-associated decline in mitochondrial respiration and biosynthetic function. In addition, treatment of young rats with acetyl-L-carnitine has a stimulating effect on liver metabolism, probably through an increase in ATP production.
Mollica
M P
MP
Department of General and Environmental Physiology, University of Naples Federico II, Italy.
Iossa
S
S
Soboll
S
S
Liverini
G
G
D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D000108:Acetylcarnitine / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D005947:Glucose / Q000096:biosynthesis; D007651:Keto Acids / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism
D007651:Keto Acids; D000108:Acetylcarnitine; D014508:Urea; D000102:Acetyl-CoA C-Acyltransferase; D005947:Glucose