title: Differential subcutaneous adipose tissue gene expression patterns in a randomized clinical trial of efavirenz or lopinavir-ritonavir in antiretroviral-naive patients.
abstract: Gene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms behind body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here, we evaluated early changes in adipose tissue gene expression and their relationship to fat changes in ART-naive HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline and weeks 16 and 48. mRNA changes of 11 genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy, and inflammation were assessed through reverse transcription-quantitative PCR (RT-qPCR). Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (P < 0.05). After 16 weeks of exposure to the drug regimen, transcripts of CEBP/A, ADIPOQ, GLUT4, LPL, and COXIV were significantly down-regulated in the EFV arm compared to the LPV/r arm (P < 0.05). Significant correlations were observed between LPL expression change and trunk fat change at week 16 in both arms and between CEBP/A or COXIV change and trunk fat change at the same time point only in the EFV arm and not in the LPV/r arm. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV and LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm. (This was a substudy of a randomized clinical trial [LIPOTAR study] registered at ClinicalTrials.gov under identifier NCT00759070.).
authors.affiliation: Group of Genomics and Pharmacogenomics in HIV, Retrovirology and Viral Immunopathogeny Laboratory, IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Egaña-Gorroño
authors.affiliation: Department of Infectious Diseases, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Martínez
authors.affiliation: Department of Infectious Diseases, Hospital de Sant Pau, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Domingo
authors.affiliation: Department of Infectious Diseases, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Loncà
authors.affiliation: Group of Genomics and Pharmacogenomics in HIV, Retrovirology and Viral Immunopathogeny Laboratory, IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Escribà
authors.affiliation: Plastic Surgery Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Fontdevila
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, IISPV, University of Rovira i Virgili, Tarragona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Vidal
authors.affiliation: Fundació Lluita Contra la SIDA, Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Negredo
authors.affiliation: Group of Genomics and Pharmacogenomics in HIV, Retrovirology and Viral Immunopathogeny Laboratory, IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain Department of Infectious Diseases, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Group of Genomics and Pharmacogenomics in HIV, Retrovirology and Viral Immunopathogeny Laboratory, IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain marnedo@clinic.ub.es.
authors.forename: M
authors.initials: M
authors.lastname: Arnedo
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000821:virology; D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D050156:Adipogenesis / Q000235:genetics*; D052242:Adiponectin / Q000096:biosynthesis; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use*; D001823:Body Composition / Q000187:drug effects*; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004338:Drug Combinations; D000068679:Emtricitabine; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D050151:Subcutaneous Fat / Q000166:cytology*; D000068698:Tenofovir
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D003521:Cyclopropanes; D004338:Drug Combinations; D051275:Glucose Transporter Type 4; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; C495692:SLC2A4 protein, human; C558899:lopinavir-ritonavir drug combination; D003841:Deoxycytidine; D061466:Lopinavir; D000068698:Tenofovir; C548261:LPL protein, human; D008071:Lipoprotein Lipase; D000068679:Emtricitabine; D005947:Glucose; D000225:Adenine; C098320:efavirenz; D019438:Ritonavir