Site specific alterations of adipose tissue mitochondria in 3′-azido-3′-deoxythymidine (AZT)-treated rats: An early stage in lipodystrophy?

Autor: Louis Casteilla, Dominique Breilh, Sylvie Caspar-Bauguil, Jean-Baptiste Gordien, Bénédicte Salin, Stéphanie Hagry, Yvette Fernandez, Audrey Carrière, Jacques Schaeffer, Michel Rigoulet, Anne Galinier, Luc Pénicaud, Bertrand Beauvoit, Catherine Deveaud
Přispěvatelé: Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31] (LMPM), IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2005
Předmět:
Zdroj: Biochemical Pharmacology
Biochemical Pharmacology, Elsevier, 2005, 70 (1), pp.90-101. ⟨10.1016/j.bcp.2005.04.015⟩
ISSN: 0006-2952
1873-2968
DOI: 10.1016/j.bcp.2005.04.015
Popis: 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.
Databáze: OpenAIRE