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Antimicrobial Agents and Chemotherapy, February 2007, p. 583-590, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.01078-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Site-Specific Reduction of Oxidative and Lipid Metabolism in Adipose Tissue of 3'-Azido-3'-Deoxythymidine-Treated Rats{triangledown}

Catherine Deveaud,* Bertrand Beauvoit, Annabel Reynaud, and Jacques Bonnet

INSERM U441, Avenue du Haut Lévêque, 33600 Pessac, France

Received 26 August 2006/ Returned for modification 9 November 2006/ Accepted 27 November 2006

Although it is well accepted that treatment with some nucleoside reverse transcriptase inhibitors modifies both fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examined whether a decrease in oxidative capacity, induced by a chronic oral administration of 3'-azido-3'-deoxythymidine (AZT) in rats, could be associated with an alteration of the lipogenic capacity of white adipose tissues. The impact of obesity as a factor was then evaluated. Results showed that AZT treatment induced differential effects depending on anatomical localization. Indeed, in the inguinal adipose tissue, the specific activities of cytochrome c oxidase and fatty acid synthase, two rate-controlling enzymes in energy and lipogenic metabolisms, respectively, both decreased under AZT treatment, thus leading to a lowered cell lipid accumulation. Moreover, the AMP-activated protein kinase phosphorylation level tended to increase, thus implying that AZT causes an energy imbalance. Furthermore, the inguinal tissue of obese rats presented a sensitivity to AZT treatment that was higher than that of lean rats. In contrast, for epididymal tissue, no significant change in all these parameters could be detected under AZT treatment, regardless of the nutritional status of the animals. Taken together, these data demonstrate differential effects of AZT on subcutaneous adipose tissue and visceral white adipose tissue. It could be considered that the chronic decreases in energy and lipogenic metabolism of inguinal adipocyte, consecutive to AZT treatment, may lead, in the long term, to adipose tissue atrophy.

* Corresponding author. Mailing address: INSERM U441, Avenue du Haut Lévêque, 33600 Pessac, France. Phone: (33) 5 57 89 19 79. Fax: (33) 5 56 36 89 79. E-mail: catherine.deveaud{at}wanadoo.fr.

{triangledown} Published ahead of print on 11 December 2006.

Antimicrobial Agents and Chemotherapy, February 2007, p. 583-590, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.01078-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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