RT Journal Article
SR Electronic
T1 Metabolic profiling of adiponectin levels in adults: Mendelian randomization analysis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 126789
DO 10.1101/126789
A1 Borges Maria Carolina
A1 Barros Aluísio JD
A1 Ferreira Diana L Santos
A1 Casas Juan Pablo
A1 Horta Bernardo Lessa
A1 Kivimaki Mika
A1 Kumari Meena
A1 Usha Menon
A1 Gaunt Tom R
A1 Ben-Shlomo Yoav
A1 Freitas Deise F
A1 Oliveira Isabel O
A1 Gentry-Maharaj Aleksandra
A1 Fourkala Evangelia
A1 Lawlor Debbie A
A1 Hingorani Aroon D
YR 2017
UL http://biorxiv.org/content/early/2017/04/13/126789.abstract
AB Background Adiponectin, a circulating adipocyte-derived protein has insulin-sensitizing, anti-inflammatory, anti-atherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown.Objectives 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 We applied multivariable regression in up to 5,906 adults and Mendelian randomization (using cis-acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analysing the causal effect of adiponectin in the metabolic profile of up to 38,058 adults. Participants were largely European from six longitudinal studies and one genome-wide association consortium.Results In the multivariable regression analyses, higher circulating adiponectin was associated with higher HDL lipids and lower VLDL 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 one study with admixed population.Conclusion Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant.