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Aims: To assess the potential direct effects of the integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human immunodeficiency virus (PLWH), on human adipose cells., Main Methods: Drugs were added to the differentiation medium of human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells and morphological adipogenesis was monitored for 10 days. Also, adipocytes were exposed to drugs following differentiation (day 14). The gene expression levels of selected adipogenesis markers, adipocyte metabolism markers, adipokines, and cytokines were determined by quantitative-reverse transcription polymerase-chain reaction. The release of adiponectin and leptin into the culture medium was measured using specific enzyme-linked immunosorbent assay, and release of interleukin-6 and chemokine (CC motif) ligand-2 using Multiplex assays., Key Findings: Overall morphological adipogenesis was unaltered by INsTIs. The expression of adipogenesis marker genes (peroxisome proliferator-activated receptor-Ɣ and lipoprotein lipase) was slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed gene expression and the release of pro-inflammatory cytokines in differentiating adipocytes. Dolutegravir and raltegravir increased interleukin-6 gene expression, but only dolutegravir increased interleukin-6 release. Dolutegravir repressed adiponectin expression and release in differentiating adipocytes and had a similar but milder effect on leptin. Drug treatment of mature adipocytes reduced adiponectin gene expression in response to dolutegravir., Significance: The INsTIs studied do not have a significant effect on human adipose cell differentiation but exert distinct effects on gene expression and secretion of adipokines and cytokines. These findings will help understand and manage the effects of INsTI-containing treatments on body weight and metabolic dysregulation in PLWH., Competing Interests: Declaration of competing interest Dr. Pere Domingo reported receiving honoraria from Merck Sharp & Dohme, Gilead Sciences, ViiV Healthcare, Janssen, Cilag, Thera technologies, and Roche. All the other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript. The authors guarantee that they have the authority to publish the work and that the manuscript and confirm that neither the manuscript nor any parts of its content are currently under consideration or published in another journal., (Copyright © 2022. Published by Elsevier Inc.)

The physiological regulation of hepatic glutathione efflux by catecholamines is poorly understood. The purpose of this work was to review the role of adrenergic receptors (AR) on total glutathione (G T ) efflux in rat liver. Two models were used: isolated hepatocytes and perfused livers. In hepatocytes 10 μM adrenaline (Adr), but not isoproterenol (Iso) a β-AR agonist, or phenylephrine (Phe) an α 1 -AR agonist, (in a Krebs-Henseleit buffer (KHB) enriched with Ca 2+ and some aminoacids) increased in 13% G T efflux. In livers perfused with KHB, Adr or Iso at 1 μmolar doses (but not Phe) stimulated 11-fold initial velocity of G T release, but only during the first 2 min of perfusion. This immediate response progressively disappeared during the following 15 min of perfusion. A second phase of G T efflux, observed between 2 and 14 min of perfusion, mimics the one reported earlier in isolated hepatocytes. The ED 50 for Adr and Iso activation are in the range of 320 nM and 10 nM, respectively. Iso-mediated G T release requires Ca 2+ to work, and was prevented by H89, glibenclamide, cystic fibrosis transmembrane regulator (CFTR) antibodies, and a direct CFTR inhibitor. This short-lived G T release system is associated to PKA activation and probably operates through CFTR., (Copyright © 2018 Elsevier Inc. All rights reserved.)