miRNA-218 Targets Lipin-1 and Glucose Transporter Type 4 Genes in 3T3-L1 Cells Treated With Lopinavir/Ritonavir

Conclusion: 3T3-L1 cells, treated with LPV/RTV, show altered lipid content due to increased miRNA-218 levels, which affects lipin-1 mRNA. Moreover, increased miRNA-218 levels were inversely correlated with changes in GLUT-4 expression, which suggests a role for miRNA-218 in mediating the insulin resistance consequent to cART. Introduction Metabolic syndrome is a serious consequence of combined Antiretroviral Therapy (cART). HIV-associated metabolic syndrome is often accompanied by lipodystrophy (LS), the redistribution of body fat with loss of subcutaneous adipose tissue in face, limbs and buttocks, concomitant with fat accumulation in the trunk and in the intra-abdominal and inter-scapular regions. These morphological alterations are associated with metabolic dysfunctions including (i) insulin-resistance, (ii) hypercholesterolemia, and (iii) hypertriglyceridemia (Reinsch et al., 2012), all of which predispose the individual to increased risks of developing cardiovascular diseases as well as type II diabetes (Costa and Almeida, 2015). The causes of HIV-associated metabolic syndrome and LS are multiple, and poorly understood. HIV itself promotes LS, by generating a local inflammation of adipose tissue (Caron-Debarle et al., 2010). Similarly, the nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) (Minami et al., 2011; Manente et al., 2012) used in cART, primarily contribute to the development of metabolic dysfunctions by promoting lipohyp...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research