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dc.contributor.authorRoman, Marius
dc.contributor.authorZakkar, Mustafa
dc.contributor.authorJoel-David, Lathishia
dc.contributor.authorKumar, Tracy
dc.contributor.authorMurphy, Gavin
dc.date.accessioned2022-02-04T14:43:57Z
dc.date.available2022-02-04T14:43:57Z
dc.date.issued2022
dc.identifier.citationAdebayo, A. S., Roman, M., Zakkar, M., Yusoff, S., Gulston, M., Joel-David, L., Anthony, B., Lai, F. Y., Murgia, A., Eagle-Hemming, B., Sheikh, S., Kumar, T., Aujla, H., Dott, W., Griffin, J. L., Murphy, G. J., & Woźniak, M. J. (2022). Gene and metabolite expression dependence on body mass index in human myocardium. Scientific reports, 12(1), 1425. https://doi.org/10.1038/s41598-022-05562-8en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12904/15167
dc.description.abstractWe 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.
dc.description.urihttps://www.nature.com/articles/s41598-022-05562-8en_US
dc.language.isoenen_US
dc.subjectcardiovascular biologyen_US
dc.subjectmetabolomicsen_US
dc.subjecttranscriptionen_US
dc.titleGene and metabolite expression dependence on body mass index in human myocardiumen_US
dc.typeArticleen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US
rioxxterms.versionNAen_US
rioxxterms.versionofrecordhttps://doi.org/10.1038/s41598-022-05562-8en_US
rioxxterms.typeJournal Article/Reviewen_US
refterms.panelUnspecifieden_US
refterms.dateFirstOnline2022-01
html.description.abstractWe 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.en_US
rioxxterms.funder.project94a427429a5bcfef7dd04c33360d80cden_US


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