December 15, 2017
Background: Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory,
antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin
in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin
concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile.
Methods and Results: We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis-acting
genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of
adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies
and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin
was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels,
branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian
randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk
groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population.
Conclusions: Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context
of metabolic disease than a key determinant.
Circulation: Cardiovascular Genetics
© 2017 The Authors
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