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Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis.
Maria Carolina Borges1, Aluísio J D Barros2, Diana L Santos Ferreira2
1From the Post-Graduate Program in Epidemiology, Federal University of Pelotas, Brazil (M.C.B., A.J.D.B., B.L.H., D.F.F., I.O.O.); MRC Integrative Epidemiology Unit (M.C.B., D.L.S.F., T.R.G., D.A.L.) and Population Health Sciences, Bristol Medical School (M.C.B., D.L.S.F., T.R.G., Y.B.-S., D.A.L.), University of Bristol, United Kingdom; Farr Institute of Health Informatics (J.P.C., A.D.H.), Department of Epidemiology and Public Health (M. Kivimaki, M. Kumari), Department of Women's Cancer, Institute for Women's Health, Faculty of Population Health Sciences (U.M., A.G.-M., E.F.), and Institute of Cardiovascular Science (A.D.H.), University College London, United Kingdom; Institute for Social and Economic Research, University of Essex, United Kingdom (M. Kumari); and Department of Physiology and Pharmacology, Institute of Biology, Federal University of Pelotas, Brazil (I.O.O.). m.c.borges@bristol.ac.uk.
Higher blood adiponectin levels correlate with a healthier metabolic profile in observational studies, but causal links are not supported by genetic analysis. Adiponectin appears to be an epiphenomenon in metabolic disease.
Area of Science:
- Metabolic disease research
- Human physiology
- Genetics and epidemiology
Background:
- Adiponectin, an adipocyte-derived protein, shows beneficial effects in animal models.
- Systemic effects of adiponectin in humans remain largely unknown.
- Investigating adiponectin's role in human metabolic health is crucial.
Purpose of the Study:
- Define the metabolic profile associated with higher adiponectin concentration in humans.
- Determine if adiponectin concentration variation causally affects the systemic metabolic profile.
Main Methods:
- Multivariable regression analysis in 5909 adults.
- Mendelian randomization using genetic variants in the adiponectin gene vicinity in 37,545 adults.
- Analysis of longitudinal studies and genome-wide association consortium data.
Main Results:
- Higher adiponectin associated with favorable lipid profiles (HDL, VLDL), lower glucose, branched-chain amino acids, and inflammatory markers in regression analyses.
- Mendelian randomization did not support most of these associations, indicating a lack of causal effect.
- Consistent findings across sexes and after excluding high-risk groups.
Conclusions:
- Circulating adiponectin concentration is likely an epiphenomenon in metabolic disease.
- Adiponectin may not be a key determinant of systemic metabolic profile in humans.
- Further research is needed to understand the complex relationship between adiponectin and metabolic health.
