title: Serum leptin level mediates the association of body composition and serum C-reactive protein in HIV-infected persons on antiretroviral therapy.
abstract: Higher body mass index (BMI) is associated with increased serum C-reactive protein (CRP) levels in HIV-infected individuals on antiretroviral therapy (ART), but the relationship of adipose tissue mass to systemic inflammation is not well described in this population. We hypothesized that serum adipokine levels (i.e., hormones produced by adipocytes) are a superior predictor of CRP compared to anthropometric or radiographic measures of body composition in patients on effective, stable ART. We evaluated the relationship of serum leptin, adiponectin, and resistin, BMI, and dual energy x-ray absorptiometry (DEXA) measurements with serum highly sensitive CRP (hsCRP) in a cross-sectional cohort of 106 predominantly virologically suppressed, HIV-infected adults on ART for ≥24 weeks using multivariable linear regression and formal criteria to assess statistical mediation. Median BMI, hsCRP, and leptin values were 25.2 kg/m(2), 3.0 mg/liter, and 3.8 ng/ml, respectively. BMI and DEXA limb fat, body fat, and trunk fat measurements were significantly associated with both serum leptin and hsCRP levels (all p≤0.02). Leptin was also associated with hsCRP (p<0.01). The regression coefficient for the effect of BMI or DEXA measurements on hsCRP was reduced, and the relationship was no longer statistically significant, after adjusting for leptin, indicating leptin functioned as a mediating variable within these relationships. Adiponectin and resistin levels did not demonstrate similar effects. Serum leptin was a superior predictor of hsCRP compared to BMI and DEXA body fat measurements, which may reflect alterations in body composition in treated HIV infection and the important contribution of adipose tissue to inflammation in this population.
authors.affiliation: Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2582, USA. john.r.koethe@vanderbilt.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Koethe
authors.forename: Aihua
authors.initials: A
authors.lastname: Bian
authors.forename: Ayumi K
authors.initials: AK
authors.lastname: Shintani
authors.forename: M Sean
authors.initials: MS
authors.lastname: Boger
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Mitchell
authors.forename: Husamettin
authors.initials: H
authors.lastname: Erdem
authors.forename: Todd
authors.initials: T
authors.lastname: Hulgan
mesh_terms: D015502:Absorptiometry, Photon; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D052242:Adiponectin / Q000097:blood*; D000273:Adipose Tissue; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001823:Body Composition; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000503:physiopathology; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D052242:Adiponectin; D019380:Anti-HIV Agents; D020738:Leptin; D002097:C-Reactive Protein