title: Site specific alterations of adipose tissue mitochondria in 3'-azido-3'-deoxythymidine (AZT)-treated rats: an early stage in lipodystrophy?
abstract: 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.
authors.affiliation: 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>
authors.forename: Catherine
authors.initials: C
authors.lastname: Deveaud
authors.forename: Bertrand
authors.initials: B
authors.lastname: Beauvoit
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hagry
authors.forename: Anne
authors.initials: A
authors.lastname: Galinier
authors.forename: Audrey
authors.initials: A
authors.lastname: Carrière
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Salin
authors.forename: Jacques
authors.initials: J
authors.lastname: Schaeffer
authors.forename: Sylvie
authors.initials: S
authors.lastname: Caspar-Bauguil
authors.forename: Yvette
authors.initials: Y
authors.lastname: Fernandez
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Gordien
authors.forename: Dominique
authors.initials: D
authors.lastname: Breilh
authors.forename: Luc
authors.initials: L
authors.lastname: Penicaud
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.forename: Michel
authors.initials: M
authors.lastname: Rigoulet
mesh_terms: 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*
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D015215:Zidovudine; D019289:Pyruvic Acid; D003576:Electron Transport Complex IV