Gene and metabolite expression dependence on body mass index in human myocardium.

Autor: Adebayo AS; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Roman M; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Zakkar M; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Yusoff S; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK.; Cardiovascular Sciences, King's College London, London, UK., Gulston M; Department of Biochemistry and Cambridge Systems Biology Centre, The Sanger Building, 80 Tennis Court Road, Cambridge, CB2 1GA, UK., Joel-David L; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Anthony B; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Lai FY; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Murgia A; Department of Biochemistry and Cambridge Systems Biology Centre, The Sanger Building, 80 Tennis Court Road, Cambridge, CB2 1GA, UK., Eagle-Hemming B; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Sheikh S; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Kumar T; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Aujla H; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Dott W; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Griffin JL; Department of Biochemistry and Cambridge Systems Biology Centre, The Sanger Building, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.; The Rowet Institute, University of Aberdeen, Aberdeen, AB24 3FX, UK., Murphy GJ; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK., Woźniak MJ; Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK. mw299@leicester.ac.uk.; Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield General Hospital, Leicester, LE3 9QP, UK. mw299@leicester.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Jan 26; Vol. 12 (1), pp. 1425. Date of Electronic Publication: 2022 Jan 26.
DOI: 10.1038/s41598-022-05562-8
Abstrakt: We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-six adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence. 120 displayed u-shape and 119 n-shape expression patterns. The identified local minima or maxima peaked at BMI 28-29. Based on these results and to best fit the WHO classification, we grouped the patients into three groups: BMI < 25, 25 ≤ BMI ≤ 32, and BMI > 32. The analysis indicated that protein translation-related pathways were downregulated in 25 ≤ BMI ≤ 32 compared with BMI < 25 patients. Muscle contraction transcripts were upregulated in 25 ≤ BMI ≤ 32 patients, and cholesterol synthesis and innate immunity transcripts were upregulated in the BMI > 32 group. Transcripts involved in translation, muscle contraction and lipid metabolism also formed distinct correlation networks with biphasic dependence on BMI. Metabolite analysis identified acylcarnitines and ribose-5-phosphate increasing in the BMI > 32 group and α-ketoglutarate increasing in the BMI < 25 group. Molecular differences in the myocardium mirror the biphasic relationship between BMI and mortality.
(© 2022. The Author(s).)
Databáze: MEDLINE
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