Prospective Relation of Circulating Adipokines to Incident Metabolic Syndrome: The Framingham Heart Study

J Am Heart Assoc. 2017 Jul 16;6(7):e004974. doi: 10.1161/JAHA.116.004974.

Abstract

Background: Adipokines are elaborated by adipose tissue and are associated with glycemic, lipid, and vascular traits. We hypothesized that in a cross-sectional analysis circulating adipokines are altered among subsets of obesity stratified by presence versus absence of metabolic syndrome (MetS) and prospectively predict the incidence of MetS.

Methods and results: Participants in the community-based Framingham Third Generation Cohort who attended examination cycle 1 were included in the study (2002-2005; N=3777, mean age, 40 years; 59% women). Circulating adiponectin, leptin, leptin receptor, fetuin-A, fatty acid-binding protein 4, and retinol binding protein 4 were assayed and related to incident MetS in follow-up (mean 6 years). The adipokines were compared among individuals with excess body weight (body mass index ≥25 kg/m2) and prevalent MetS, excess body weight without MetS (metabolically healthy obese), and normal-weight with MetS (metabolically obese, normal-weight) with normal-weight participants without MetS as a referent. Metabolically healthy obese individuals (n=1467) had higher circulating levels of fetuin-A and fatty acid-binding protein 4 but lower levels of leptin, leptin receptor, and adiponectin (P<0.001 for all). The adipokine panel was associated with incident MetS (263 new-onset cases; P=0.002). Higher circulating concentrations of retinol-binding protein 4 and fetuin-A were associated with incidence of MetS (odds ratio per 1-SD increment log marker, 1.21; 95% CI, 1.03-1.41 [P=0.02] and 1.17; 95% CI, 1.01-1.34 [P=0.03], respectively).

Conclusions: In our community-based sample of young to middle-aged adults, metabolically healthy obese individuals demonstrated an adverse adipokine profile. Higher circulating levels of retinol-binding protein 4 and fetuin-A marked future cardiometabolic risk.

Keywords: adipokine; epidemiology; metabolic syndrome; obesity; risk factor.

MeSH terms

  • Adipokines / blood*
  • Adiponectin / blood
  • Adult
  • Biomarkers / blood
  • Chi-Square Distribution
  • Cross-Sectional Studies
  • Fatty Acid-Binding Proteins / blood
  • Female
  • Humans
  • Incidence
  • Leptin / blood
  • Logistic Models
  • Longitudinal Studies
  • Male
  • Massachusetts / epidemiology
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / diagnosis
  • Metabolic Syndrome / epidemiology*
  • Middle Aged
  • Multivariate Analysis
  • Obesity / blood*
  • Obesity / diagnosis
  • Obesity / epidemiology*
  • Odds Ratio
  • Prospective Studies
  • Receptors, Leptin / blood
  • Retinol-Binding Proteins, Plasma / analysis
  • Risk Factors
  • alpha-2-HS-Glycoprotein / analysis

Substances

  • ADIPOQ protein, human
  • AHSG protein, human
  • Adipokines
  • Adiponectin
  • Biomarkers
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • LEPR protein, human
  • Leptin
  • RBP4 protein, human
  • Receptors, Leptin
  • Retinol-Binding Proteins, Plasma
  • alpha-2-HS-Glycoprotein