Effect of dehydroepiandrosterone sulfate on carnitine acetyl transferase activity and L-carnitine levels in oophorectomized rats.
Alteration in energy metabolism of postmenopausal women might be related to the reduction of dehydroepiandrosterone sulfate (DHEAS). DHEA and DHEAS decline with age, leveling at their nadir near menopause. DHEA and DHEAS modulate fatty acid metabolism by regulating carnitine acyltransferases and CoA. The purpose of this study was to determine whether dietary supplementation with DHEAS would also increase tissue L-carnitine levels, carnitine acetyltransferase (CAT) activity and mitochondrial respiration in oophorectomized rats. Plasma L-carnitine levels rose following oophorectomy in all groups (P < 0.0001). Supplementation with DHEAS was not associated with further elevation of plasma L-carnitine levels, but with increased hepatic total and free L-carnitine (P = 0.021 and P < 0.0001, respectively) and cardiac total L-carnitine concentrations (P = 0.045). In addition, DHEAS supplementation increased both hepatic and cardiac CAT activities (P < 0.0001 and P = 0.05 respectively). CAT activity positively correlated with the total and free carnitine levels in both liver and heart (r = 0.764, r = 0.785 and r = 0.700, r = 0.519, respectively). Liver mitochondrial respiratory control ratio, ADP:O ratio and oxygen uptake were similar in both control and supplemented groups. These results demonstrate that in oophorectomized rats, dietary DHEAS supplementation increases the liver and heart L-carnitine levels and CAT activities. In conclusion, DHEAS may modulate L-carnitine level and CAT activity in estrogen deficient rats. The potential role of DHEAS in the regulation of fatty acid oxidation in postmenopausal women is worthy of investigation.
Chiu
K M
KM
Institute of Aging/Department of Medicine, University of Wisconsin-Madison, USA.
Schmidt
M J
MJ
Shug
A L
AL
Binkley
N
N
Gravenstein
S
S
D000818:Animals; D002331:Carnitine / Q000378:metabolism*; D002332:Carnitine O-Acetyltransferase / Q000097:blood / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010052:Ovariectomy; D010101:Oxygen Consumption; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000378:metabolism; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
D013386:Succinates; D012402:Rotenone; D019314:Dehydroepiandrosterone Sulfate; D019802:Succinic Acid; D002332:Carnitine O-Acetyltransferase; D002331:Carnitine