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Circulating Ghrelin, Leptin, and Soluble Leptin Receptor Concentrations and Cardiometabolic Risk Factors in a Community-Based Sample

The Framingham Study (E.I., M.G.L., X.Y., T.J.W., E.J.B., R.S.V.), Boston University School of Medicine, Framingham, Massachusetts 01702-5803; Department of Medical Epidemiology and Biostatistics (E.I.), Karolinska Institutet, SE-171 77 Stockholm, Sweden; Department of Mathematics and Statistics (M.G.L.), Boston University, and Evans Memorial Department of Medicine and Whitaker Cardiovascular Institute (I.L., E.J.B., R.S.V.), Boston University School of Medicine, Boston, Massachusetts 02215; Department of Biostatistics (X.Y.), Boston University School of Public Health, Boston, Massachusetts 02118; Massachusetts General Hospital and Harvard Medical School (T.J.W.) and Department of Medicine (J.B.M.), Massachusetts General Hospital, Boston, Massachusetts 02114; and Division of Cardiovascular Medicine (J.F.K.), University of Massachusetts Medical School, Worcester, Massachusetts 01655

Address all correspondence and requests for reprints to: Ramachandran S. Vasan, M.D., F.A.C.C., Framingham Heart Study, 73 Mount Wayte Avenue, Suite 2, Framingham, Massachusetts 01702-5803. E-mail: vasan{at}bu.edu.

Context: The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown.

Objective: The objective of the study was to study the cross-sectional relations of these adipokines to cardiometabolic risk factors in a community-based sample.

Design, Setting, and Participants: We measured circulating ghrelin, leptin, and sOB-R in 362 participants (mean age 45 yr; 54% women) of the Framingham Third Generation Cohort.

Main Outcome Measures: Body mass index, waist circumference (WC), blood pressure, lipid measures, fasting glucose, smoking, and metabolic syndrome (MetS) were measured.

Results: Ghrelin and leptin concentrations were significantly higher in women (P < 0.0001). In multivariable models, ghrelin was inversely associated with age and systolic blood pressure, and leptin was positively related to body mass index and WC. sOB-R was positively associated with age, total cholesterol, and fasting glucose and inversely with WC and high-density lipoprotein cholesterol. Ghrelin and sOB-R concentrations were significantly lower with number of MetS components (P for trend = 0.022 and < 0.0001, respectively), whereas leptin concentrations were higher (P for trend = 0.0001). Relating all adipokines to MetS conjointly, higher ghrelin and leptin concentrations were associated with decreased and increased odds of MetS (odds ratio 0.55, P < 0.0001; odds ratio 4.44, P = 0.0002, per 1 SD increase of respective log adipokine).

Conclusions: In our community-based sample, we observed a sexual dimorphism in circulating ghrelin and leptin concentrations. Ghrelin, leptin, and sOB-R were associated with number of MetS components cross-sectionally, consistent with the hypothesis that these adipokines may have a central role in cardiometabolic risk.