title: Changes in Inflammation, Oxidative Stress, Mitochondrial DNA Content after Rosiglitazone in HIV Lipoatrophy.
abstract: OBJECTIVE: We aim to evaluate the mechanisms of rosiglitazone-induced fat recovery in HIV+ patients with lipoatrophy on thymidine Nucleoside Reverse Transcriptase Inhibitors (NRTI) sparing regimens.  METHOD: Measures of limb fat (DXA), oxidative stress (F2 isoprostanes) and inflammation [High-sensitivity C-reactive protein (hsCRP), soluble Tumor Necrosis Factor Receptors (sTNFR)-I, sTNFR-II, and interleukin (IL)-6] were performed. Gluteal fat mitochondrial DNA (mtDNA) and peroxisome proliferator-activated receptor (PPAR)-γ RNA [expressed as PPAR-γ/Glyceraldehyde 6-Phosphate Dehydrogenase (GAPDH) RNA ratio] were measured by quantitative PCR.  RESULT: 71 patients on thymidine NRTI-sparing regimens were randomized to rosiglitazone vs. placebo for 48 weeks. Duration off thymidine NRTIs was similar between groups. From week 0-48, limb fat increased significantly (p=0.02) more in the rosiglitazone than in the placebo group. Within both groups, F2-isoprostanes, sTNFR-I and sTNFR-II increased significantly (p ≤ 0.003), hsCRP decreased significantly (≤ 0.02), and IL-6 did not change. No differences were seen between groups in any of the inflammation markers. Fat mtDNA (copies/cell) increased nonsignificantly: +41(p=0.08) and +29(p=0.38) within rosiglitazone and placebo group; respectively. PPAR-γ/GAPDH ratio did not change within or between groups.  CONCLUSION: Limb fat improvements seen after rosiglitazone were not associated with changes in mtDNA, oxidative or inflammation markers, or PPAR-γ expression. F2 isoprostanes and some of the inflammation markers worsened over time in these subjects on stable ART, regardless of the rosiglitazone assignment. Thus, lipoatrophy can be in part overcome by a separate pathway independent of mitochondrial DNA depletion, such as PPAR-γ.
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Marisa
authors.initials: M
authors.lastname: Tungsiripat
authors.forename: Dalia
authors.initials: D
authors.lastname: El-Bejjani
authors.forename: Nesrine
authors.initials: N
authors.lastname: Rizk
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Allison C
authors.initials: AC
authors.lastname: Ross
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Walker
authors.forename: Dirk
authors.initials: D
authors.lastname: Lebrecht
authors.forename: Ginger
authors.initials: G
authors.lastname: Milne
authors.forename: Norma
authors.initials: N
authors.lastname: Storer
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey