Site specific alterations of adipose tissue mitochondria in 3'-azido-3'-deoxythymidine (AZT)-treated rats: an early stage in lipodystrophy?
Although it is well accepted that treatment with nucleoside reverse transcriptase inhibitors (NRTIs) modifies fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examines the effects of chronic oral administration of 3'-azido-3'-deoxythymidine (AZT) on the mitochondrial metabolism and the redox status management of rat white adipose tissues originating from two anatomical sites, as well as of the rat liver. Results showed that AZT treatment induced differential effects on the mitochondrial functions depending on the anatomical localisation. Indeed, in inguinal adipose tissue, a significant decrease in the cytochrome c oxidase activity and in the mitochondrial DNA (mtDNA) content was observed, whereas the activity of citrate synthase, a mitochondrial protein exclusively encoded by the nucleus, was not affected. In contrast, no significant change in these parameters could be detected for epididymal tissue and for liver. In parallel, no oxidative stress could be detected after treatment, for both white adipose tissues and for liver, even though treated liver exhibited several modifications in redox management. Taken together, these data demonstrate differential mitochondrial effects of AZT on subcutaneous versus visceral white adipose tissue. Moreover, the decrease in mitochondrial oxidative capacity of inguinal adipocyte consecutive to AZT treatment is not primarily due to an oxidative stress per se, but rather to a depletion of the mtDNA content per cell.
Deveaud
Catherine
C
Institut de Biochimie et de Génétique Cellulaires, UMR 5095 CNRS-Université Victor Ségalen, 1 rue Camille Saint Saëns, 33077 Bordeaux Cedex, France. Catherine.Deveaud@wanadoo.fr <Catherine.Deveaud@wanadoo.fr>
Beauvoit
Bertrand
B
Hagry
Stéphanie
S
Galinier
Anne
A
Carrière
Audrey
A
Salin
Bénédicte
B
Schaeffer
Jacques
J
Caspar-Bauguil
Sylvie
S
Fernandez
Yvette
Y
Gordien
Jean-Baptiste
JB
Breilh
Dominique
D
Penicaud
Luc
L
Casteilla
Louis
L
Rigoulet
Michel
M
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019380:Anti-HIV Agents / Q000633:toxicity*; D004272:DNA, Mitochondrial / Q000032:analysis; D003576:Electron Transport Complex IV / Q000378:metabolism; D039682:HIV-Associated Lipodystrophy Syndrome / Q000209:etiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019289:Pyruvic Acid / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects; D015215:Zidovudine / Q000633:toxicity*
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D015215:Zidovudine; D019289:Pyruvic Acid; D003576:Electron Transport Complex IV