Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function

Biochem Pharmacol. 2023 Dec 26:116010. doi: 10.1016/j.bcp.2023.116010. Online ahead of print.ABSTRACTCombined antiretroviral therapy (cART) has been associated with increased body weight accompanied by metabolic alterations in people living with human immunodeficiency virus (PLWH). To gain insight into the combined effects of cART components on adipocyte dysfunction, we assessed whether and how treatment of human adipocytes with dolutegravir (DTG) and the nucleotide-analog reverse-transcriptase inhibitors (NRTIs), tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF), alone and in combination, altered biological processes related to adipose tissue dysfunction. DTG, TAF, and TDF were applied to human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells during differentiation (day 10) and ensuing differentiation (day 14). Selected gene markers expression was determined by qPCR, the release of adipokines and inflammatory cytokines to the culture media were assessed, and cell respiration was measured. Adipogenesis was not altered by the combined treatment of human adipocytes. However, DTG at the highest dose repressed adipogenesis marker genes expression, and TAF and TDF appeared to increase this effect. Thus, DTG repressed the expression of adiponectin and the release of adiponectin and leptin in differentiating adipocytes, and these effects were decreased in combination with TAF and TDF. DTG plus TAF or TDF on human adipocytes enhanced inflammation and stress and i...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research