Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis

Maria Carolina Borges*, Aluísio J.D. Barros, Diana L Santos Ferreira, Juan Pablo Casas, Bernardo Lessa Horta, Mika Kivimaki, Meena Kumari, Usha Menon, Tom R. Gaunt, Yoav Ben-Shlomo, Deise F. Freitas, Isabel O. Oliveira, Aleksandra Gentry-Maharaj, Evangelia Fourkala, Debbie A. Lawlor, Aroon D. Hingorani

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

10 Citations (Scopus)
424 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article numbere001837
Number of pages36
JournalCirculation: Cardiovascular Genetics
Volume10
Issue number6
Early online date13 Dec 2017
DOIs
Publication statusPublished - Dec 2017

Keywords

  • adiponectin
  • cardiovascular disease
  • insulin
  • Mendelian Randomization Analysis
  • metabolism
  • metabolomics

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