title: Differentially altered molecular signature of visceral adipose tissue in HIV-1-associated lipodystrophy.
abstract: OBJECTIVE
  Lipodystrophy in HIV-1-infected antiretroviral-treated patients is often associated with opposite alterations in adipose tissue depots as follows: lipoatrophy of subcutaneous adipose tissue (SAT) versus lipohypertrophy of visceral adipose tissue (VAT). We determined the specific molecular alterations in VAT relative to SAT in patients.
  
  
  METHODS
  We analyzed the expression of marker genes of mitochondrial function, adipogenesis, and inflammation in a unique collection of 8 biopsies of omental VAT from HIV-1-infected antiretroviral-treated patients with lipodystrophy. For comparison, we analyzed SAT from 10 patients, and SAT and VAT from 10 noninfected individuals.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction of mitochondrial DNA and gene transcripts; immunoblot and multiplex for quantification of specific proteins.
  
  
  RESULTS
  Similar mitochondrial DNA depletion and abnormal increases in mitochondrial protein levels were found in VAT and SAT from patients. Transcript levels of adipogenesis and metabolism marker genes were unaltered in VAT but were decreased in SAT. Tumor necrosis factor α and CD68 were similarly induced in both adipose depots from patients, but other markers of inflammation-related pathways showed distinct alterations as follows: interleukin 18 and interleukin 1 receptor antagonist were induced only in SAT, whereas interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 expression was reduced in VAT but not in SAT.
  
  
  CONCLUSIONS
  Mitochondrial alterations are similar in VAT and SAT from patients, whereas adipogenic gene expression is decreased in SAT but unaltered in VAT, highlighting the relevance of adipogenic processes in the differential alterations of fat depots. Specific disturbances in inflammatory status in VAT relative to SAT are present. Milder induction of proinflammatory signaling in VAT could be involved in preventing fat wasting in this depot.
authors.affiliation: *Department of Biochemistry and Molecular Biology; and †Institut de Biomedicina (IBUB), University of Barcelona, Barcelona, Spain; ‡CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain; §Red de Investigación en SIDA (RIS), Barcelona, Spain; and Departments of ‖Infectious Diseases; ¶General Surgery; and #Dermatology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Gallego-Escuredo
authors.forename: Joan
authors.initials: J
authors.lastname: Villarroya
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Eduard M
authors.initials: EM
authors.lastname: Targarona
authors.forename: Marta
authors.initials: M
authors.lastname: Alegre
authors.forename: Joan C
authors.initials: JC
authors.lastname: Domingo
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
authors.forename: Marta
authors.initials: M
authors.lastname: Giralt
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D039682:HIV-Associated Lipodystrophy Syndrome / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins