Ž . Biochimica et Biophysica Acta 1344 1997 201–209 Effect of dehydroepiandrosterone sulfate on carnitine acetyl transferase activity and L-carnitine levels in oophorectomized rats 1,2 Kit Mui Chiu a , Mary J. Schmidt b , Austin L. Shug b,c , Neil Binkley a , Stefan Gravenstein a, ) a Institute on Aging r Department of Medicine, UniÕersity of Wisconsin-Madison, and the Wm. S. Middleton VA GRECC, Madison, WI 53706, USA b Metabolic Analysis Laboratories, Inc., Madison, WI 53713, USA c Department of Neurology, UniÕersity of Wisconsin, Madison, WI 53706, USA Received 8 April 1996; revised 7 August 1996; accepted 11 September 1996 Abstract Alteration in energy metabolism of postmenopausal women might be related to the reduction of dehydroepiandrosterone Ž . 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 acetyltrans- Ž . ferase CAT activity and mitochondrial respiration in oophorectomized rats. Plasma L-carnitine levels rose following Ž . oophorectomy in all groups P - 0.0001 . Supplementation with DHEAS was not associated with further elevation of Ž . plasma L-carnitine levels, but with increased hepatic total and free L-carnitine P s 0.021 and P - 0.0001, respectively and Ž . cardiac total L-carnitine concentrations P s 0.045 . In addition, DHEAS supplementation increased both hepatic and Ž . cardiac CAT activities P - 0.0001 and P s 0.05 respectively . CAT activity positively correlated with the total and free Ž . carnitine levels in both liver and heart r s 0.764, r s 0.785 and r s 0.700, r s 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. Keywords: Dehydroepiandrosterone; L-Carnitine; Carnitine acetyl transferase; Mitochondrial function; Oophorectomy; Postmenopause ) Corresponding author. Cro Linda Parish, Eastern Virginia Medical School, Department of Internal Medicine, Hofheimer Hall, 825 Fairfax Avenue, Norfolk, VA 23507-1912, USA. Fax: Ž . q1 804 4465242; E-mail: sgravens@intmed1.evms.edu. 1 Ž . This is VA Madison GRECC publication a96-11 . 2 Part of the data have been submitted as an abstract to 1994 annual scientific meeting of the American Geriatrics Society. 1. Introduction Resting metabolic rate does not change with age in wx healthy premenopausal women 1 . However, resting metabolic rate declines during the normal menopausal transition and continues to decline thereafter. This change is also associated with the accelerated loss of fat-free mass, and an increased central fat accumula- 0005-2760r97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S0005-2760 96 00141-5