title: Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy.
abstract: OBJECTIVE
  Adipocytokines, secreted by adipose tissue, may regulate fat metabolism, lipid and glucose homeostasis and insulin sensitivity. We analysed the relations between circulating concentrations of adiponectin, leptin, interleukin-6, tumor necrosis factor alpha and its soluble receptors sTNFR1 and R2, lipodystrophic phenotypes and metabolic alterations in patients under highly active antiretroviral therapy (HAART).
  
  
  METHODS
  We studied 131 consecutive HIV-infected males under protease inhibitor (PI)-based HAART, with body mass index < 27 kg/m2 and C-reactive protein (CRP) < 10 mg/l. Patients were classified in four groups according to clinical examination: no lipodystrophy (NL), lipohypertrophy (LH), lipoatrophy (LA) and mixed lipodystrophy (ML). In addition to adipocytokines, we measured plasma fasting levels of triglycerides, cholesterol, cardiovascular risk markers (high-sensitivity CRP and apolipoproteins B/A1 ratio), fasted and 2 h post-glucose loading glycemia and insulinemia and calculated the quantitative insulin sensitivity check index.
  
  
  RESULTS
  The patients were HIV-infected and PI-treated for a mean of 8.2 and 1.6 years respectively; 74% presented lipodystrophy, 38% altered glucose tolerance and 42% hypertriglyceridemia. Insulin sensitivity correlated positively with adiponectin and negatively with leptin and interleukin-6. Adiponectin, but not leptin, negatively correlated with all metabolic parameters. Insulin resistance, metabolic defects and cardiovascular risk markers were strongly negatively correlated with the adiponectin/leptin ratio (A/L), and positively with sTNFR1. LA patients had a longer duration of infection but ML patients presented the most severe metabolic alterations, insulin resistance and A/L decrease.
  
  
  CONCLUSIONS
  These results suggest that adiponectin and the TNFalpha system are related to lipodystrophy, insulin resistance and metabolic alterations in patients under PI-based HAART. A/L and sTNFR1 could predict insulin sensitivity and potential cardiovascular risk in these patients.
authors.affiliation: INSERM U.402, Faculté de Médecine Saint-Antoine, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Vigouroux
authors.forename: Mustapha
authors.initials: M
authors.lastname: Maachi
authors.forename: Thu-Huyen
authors.initials: TH
authors.lastname: Nguyên
authors.forename: Christiane
authors.initials: C
authors.lastname: Coussieu
authors.forename: Shahin
authors.initials: S
authors.lastname: Gharakhanian
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Willy
authors.initials: W
authors.lastname: Rozenbaum
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Bastard
mesh_terms: D052242:Adiponectin; D000273:Adipose Tissue / Q000276:immunology*; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D001054:Apolipoproteins A / Q000032:analysis; D001055:Apolipoproteins B / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D052242:Adiponectin; D019380:Anti-HIV Agents; D015703:Antigens, CD; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D020738:Leptin; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D002784:Cholesterol