Mechanisms of antiretroviral-induced mitochondrial dysfunction in adipocytes and adipose tissue: in-vitro, animal and human adipose tissue studies.

PURPOSE OF REVIEW

Mitochondrial dysfunction is a major etiopathogenic event suspected to cause lipodystrophy in HIV-1-infected patients undergoing antiretroviral treatment. As adipose tissue is the main tissue affected, the present review provides an up-to-date evaluation of the evidence for mitochondrial alterations elicited by antiretroviral therapy, specifically in adipose tissue, and the potential of these abnormalities to elicit the multiple features of the lipodystrophy syndrome.

RECENT FINDINGS

Mitochondrial DNA depletion in adipose tissue is a well established effect of nucleoside-analog reverse transcriptase inhibitors. Thus, impaired mitochondrial oxidative activity is expected as a consequence of antiretroviral therapy. Recent findings, however, indicate a more complex view of antiretroviral-induced mitochondrial toxicity in adipose tissue, which may involve aspects ranging from enhanced mitochondrial reactive oxygen species production to alterations in mitochondrially driven apoptosis. The interaction of nucleoside-analog reverse transcriptase inhibitors with other drug families like protease inhibitors, as well as with the local inflammatory status of adipose tissue in HIV-1-infected patients, may account for the complex adipose mitochondrial disturbances in lipodystrophy. Moreover, mitochondrial activity in adipocytes may influence the release of regulatory adipokines.

SUMMARY

Complex mitochondrial disturbances in adipose tissue elicited by antiretroviral therapy may lead to lipoatrophy and have overall consequences in systemic metabolism via alterations in adipokine release.