Aslan T. Turer

To determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs. There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis. Nineteen patients referred for cardiac catheterization were enrolled. Peripheral and selective coronary sinus (CS) blood sampling was performed at serial timepoints following the initiation of pacing, and metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS). Pacing-stress resulted in a 225% increase in the median rate·pressure product from baseline. Increased myocardial work induced significant changes in the peripheral concentration of 43 of 125 metabolites assayed, including large changes in purine [adenosine (+99%, p = 0.006), ADP (+42%, p = 0.01), AMP (+79%, p = 0.004), GDP (+69%, p = 0.003), GMP (+58%, p = 0.01), IMP (+50%, p = 0.03), xanthine (+61%, p = 0.0006)], and several bile acid metabolites. The CS changes in metabolites qualitatively mirrored those in the peripheral blood in both timing and magnitude, suggesting the heart was not the major source of the metabolite release. Isolated increases in myocardial work can induce changes in the plasma metabolome, but these changes do not appear to be directly cardiac in origin. A number of these dynamic metabolites have known signaling functions. Our study provides additional evidence to a growing body of literature on metabolic ‘cross-talk’ between the heart and other organs.

Adiponectin is an adipocyte-derived secretory protein that has been very widely studied over the past 15 years. A multitude of different functions have been attributed to this adipokine. It has been characterised in vitro at the level of tissue culture systems and in vivo through genetic manipulation of rodent models. It is also widely accepted as a biomarker in clinical studies. Originating in adipose tissue, generally positive metabolic effects have been attributed to adiponectin. In this review, we briefly discuss the key characteristics of this interesting but very complex molecule, highlight recent results in the context of its mechanism of action and summarise some of the key epidemiological data that helped establish adiponectin as a robust biomarker for insulin sensitivity, cardiovascular disease and many additional disease phenomena.

Previous small case-control studies have suggested an inverse relationship between adiponectin and hepatic steatosis, but whether this finding is independent of insulin sensitivity and other intraabdominal fat depots is unclear. OBJECTIVES AND MAIN OUTCOME MEASURES: The objective of this study was to establish whether an independent relationship exists between serum adiponectin concentrations and liver fat. Adiponectin levels were compared with hepatic triglyceride content (HTGC) as assessed by proton magnetic resonance spectroscopy in 2215 participants from the Dallas Heart Study. Multivariate modeling was performed to control for the effects of intraabdominal fat, insulin sensitivity, and other baseline factors. In unadjusted analysis, adiponectin levels displayed inverse correlations with the amount of intraabdominal fat and HTGC. After multivariate adjustment, including individual intraabdominal fat depots and homeostasis model assessment of insulin resistance, HTGC remained significantly associated with adiponectin levels (β = -1.46, P < 0.0001 for women; β = -1.81, P < 0.0001 for men). Race- and gender-specific models demonstrated that this association was consistent across groups, except for Hispanic men. The adjusted odds ratio for hepatic steatosis (HTGC > 5.5%) per 1-sd increase in adiponectin concentrations was 0.64 (95% confidence interval = 0.52-0.78) for women and 0.61 (95% confidence interval = 0.51-0.74) for men. Data from a large, multiethnic population-based cohort show adiponectin levels are inversely associated with hepatic steatosis even after controlling for measures of insulin sensitivity, extrahepatic abdominal adiposity, and ethnicity. The mechanistic underpinnings of this association warrant further exploration.

Aims/hypothesis Plasma levels of adiponectin are inversely associated with body mass. We hypothesised that adipose tissue distribution and body composition influences adiponectin levels. Methods We assessed plasma adiponectin concentrations and dual-energy X-ray absorptiometry (DEXA) measurements of body composition among 2,820 participants from the Dallas Heart Study. Results Among both women and men, adiponectin levels were higher in whites than in either Hispanics or African-Americans (for women: median 9.99 μg/ml [25th,75th percentile 7.11, 13.77] vs 7.56 μg/ml [5.05, 9.98] vs 6.39 μg/ml [4.37, 9.41], respectively, p < 0.0001; for men: 6.43 μg/ml [4.66, 9.19] vs 5.55 μg/ml [3.64, 7.50] vs 5.03 μg/ml [3.39, 7.28], p < 0.0001). In univariate analysis, each individual component of body mass was inversely associated with adiponectin. After multivariate analysis, adiponectin levels were found to be positively associated with lower extremity fat, whether expressed in absolute mass (for women: β = 0.055, p < 0.0001; for men: β = 0.061, p < 0.0001), or as a relative proportion (for women: β = 0.035, p < 0.0001; for men: β = 0.034, p < 0.0001). This association was consistent across ethnicities. Conversely, adiponectin was negatively correlated with truncal fat, both in absolute (for women: β = −0.039, p < 0.0001; for men: β = −0.044, p < 0.0001) and relative terms (for women: β = −0.027, p < 0.0001; for men β = −0.033, p < 0.0001). At the extreme of body mass, higher degrees of lower extremity and truncal adiposity were associated with higher levels of adiponectin. Conclusions/interpretation These data suggest that the location of adipose depots differentially influences circulating adiponectin concentrations—a finding observed across ethnicity and sex. Gross measures of body mass alone do not adequately account for adiponectin levels. This supports a role of adiponectin as a mediator of the positive effects of lower extremity adiposity on improvements in insulin sensitivity.