High Molecular Weight Form of Adiponectin in Antiretroviral Drug-induced Dyslipidemia in HIV-Infected Japanese Individuals Based on in vivo and in vitro Analyses

Abstract

Objective High molecular weight (HMW)-adiponectin has been found to be a better negative regulator of insulin resistance than total adiponectin. The aim of this study was to investigate the influence of HMW-adiponectin on antiretroviral therapy (ART)-induced dyslipidemia in Japanese human immunodeficiency virus (HIV)-infected individuals. We also examined the effect of some antiretroviral drugs (ARVs) on adipocytes in vitro.
Patients and Methods Fifty-seven HIV-infected patients were enrolled in four clinical groups; (I) patients who started ART containing efavirenz (EFV); (II) patients who started ART containing a protease inhibitor without atazanavir (ATV); (III) patients who started ART containing ATV; (IV) patients who switched from ART without ATV into ART containing ATV. We measured the serum HMW-adiponectin before and one year after starting or changing ART, using an enzyme-linked immunoSorbent assay (ELISA). Furthermore, we treated the mouse adipocytes (3T3-L1) with some ARVs. The lipid content was assessed using Oil Red O staining. The expression of adiponectin was measured by quantitative real-time PCR.
Results The serum HMW-adiponectin decreased significantly in groups (I) and (II) after starting ART, and increased significantly in group (IV) after changing from ART without ATV to ART with ART. EFV, ritonavir (RTV) and nelfinavir (NFV) inhibited the expression of adiponectin mRNA in mature 3T3-L1 and to a greater extent in pre-mature 3T3-L1. This phenomenon was reversible when ARV was changed to ATV.
Conclusion Effects of the ARVs on adiponectin may vary depending on the administration of different drugs. These data suggest that the distinct metabolic effects of ARV could therefore be a consequence of their differential effects on the production of adiponectin.