title: In treatment-naïve and antiretroviral-treated subjects with HIV, reduced plasma adiponectin is associated with a reduced fractional clearance rate of VLDL, IDL and LDL apolipoprotein B-100.
abstract: OBJECTIVE
  We hypothesised that loss of peripheral fat in HIV patients would result in decreased plasma adipocytokines, in particular adiponectin, and that this decrease would be associated with changes in VLDL, IDL and LDL apolipoprotein B kinetics.
  
  
  METHODS
  Plasma adiponectin, leptin and other cytokines were measured in uninfected control subjects (n=12) and three HIV-positive groups comprising treatment-naïve patients (n=15) and patients on triple antiretroviral therapy containing protease inhibitors (PI, n=15) or non-nucleoside reverse transcriptase inhibitors (NNRTI, n=25). VLDL, IDL and LDL apolipoprotein B kinetics were measured with an infusion of [1-(13)C] leucine. Regional body fat was measured with a dual energy X-ray absorptiometry scan. Insulin resistance was calculated using homeostasis model assessment (HOMA).
  
  
  RESULTS
  Adiponectin (median [interquartile range]) was reduced in the treatment-naive (5.4 microg/ml [4.7-8.5]), PI (5.0 microg/ml [3.3-6.4]) and NNRTI (5.0 microg/ml [3.1-6.7]) groups compared with controls (9.7 microg/ml [6.9-13.3]) (p<0.05). In all subjects adiponectin correlated positively with HDL-cholesterol levels, the VLDL, IDL and LDL apolipoprotein B fractional clearance rates, and with the limb fat:lean body mass ratio (all p<0.01). Adiponectin correlated negatively with plasma triglyceride levels and HOMA (p<0.001). In a linear regression model that included HOMA, adiponectin was an independent predictor of VLDL and HDL-cholesterol levels and the IDL fractional clearance rate. TNF was higher in treatment-naive and PI subjects, and soluble TNF receptor superfamily, members 1A and 1B (previously known as TNF receptors 1 and 2) was higher in PI patients than in control subjects (p<0.05).
  
  
  CONCLUSIONS
  Adiponectin levels are significantly reduced in treated and untreated HIV patients and are predictive of VLDL and IDL apolipoprotein B fractional clearance rates. Adiponectin may have a direct effect on lipoprotein metabolism, which may be independent of insulin.
authors.affiliation: Department of HIV, Chemical Pathology and Nuclear Medicine, University Hospitals Birmingham, Birmingham, UK. satyajit.das@coventrypct.nhs.uk
authors.forename: S
authors.initials: S
authors.lastname: Das
authors.forename: M
authors.initials: M
authors.lastname: Shahmanesh
authors.forename: M
authors.initials: M
authors.lastname: Stolinski
authors.forename: F
authors.initials: F
authors.lastname: Shojaee-Moradie
authors.forename: W
authors.initials: W
authors.lastname: Jefferson
authors.forename: N C
authors.initials: NC
authors.lastname: Jackson
authors.forename: M
authors.initials: M
authors.lastname: Cobbold
authors.forename: P
authors.initials: P
authors.lastname: Nightingale
authors.forename: A M
authors.initials: AM
authors.lastname: Umpleby
mesh_terms: D052242:Adiponectin / Q000097:blood*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D053299:Apolipoprotein B-100 / Q000097:blood*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood*; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood*
chemical_list: D052242:Adiponectin; D044966:Anti-Retroviral Agents; D053299:Apolipoprotein B-100; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C030104:lipoprotein cholesterol; D002784:Cholesterol