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

Adewale S. Adebayo; Marius Roman; Mustafa Zakkar; Syabira Yusoff; Melanie Gulston; Lathishia Joel-David; Bony Anthony; Florence Y. Lai; Antonio Murgia; Bryony Eagle-Hemming; Sophia Sheikh; Tracy Kumar; Hardeep Aujla; Will Dott; Julian L. Griffin; Gavin J. Murphy; Marcin J. Woźniak

doi:10.1038/s41598-022-05562-8

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

Adewale S. Adebayo, Marius Roman, Mustafa Zakkar, Syabira Yusoff, Melanie Gulston, Lathishia Joel-David, Bony Anthony, Florence Y. Lai, Antonio Murgia, Bryony Eagle-Hemming, Sophia Sheikh, Tracy Kumar, Hardeep Aujla, Will Dott, Julian L. Griffin, Gavin J. Murphy, Marcin J. Woźniak^*

^*Corresponding author for this work

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Article number	1425
Number of pages	13
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-05562-8
Publication status	Published - Jan 2022

Bibliographical note

Funding
Van Geest Foundation, Leicester NIHR Biomedical Research Centre, British Heart Foundation CH/12/1/29419, AA18/3/34220.
Competing interests
Mrs. Kumar, Prof. Murphy and Dr Woźniak received a grant from Zimmer Biomet. Dr Murphy also received grants from Terumo and Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Data Availability Statement

Supplementary Information The online version contains supplementary material available at https://doi.org/10.1038/s41598-022-05562-8.

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Adebayo, 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), Article 1425. https://doi.org/10.1038/s41598-022-05562-8

Adebayo, AS, Roman, M, Zakkar, M, Yusoff, S, Gulston, M, Joel-David, L, Anthony, B, Lai, FY, Murgia, A, Eagle-Hemming, B, Sheikh, S, Kumar, T, Aujla, H, Dott, W, Griffin, JL, Murphy, GJ & Woźniak, MJ 2022, 'Gene and metabolite expression dependence on body mass index in human myocardium', Scientific Reports, vol. 12, no. 1, 1425. https://doi.org/10.1038/s41598-022-05562-8

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title = "Gene and metabolite expression dependence on body mass index in human myocardium",

abstract = "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.",

author = "Adebayo, {Adewale S.} and Marius Roman and Mustafa Zakkar and Syabira Yusoff and Melanie Gulston and Lathishia Joel-David and Bony Anthony and Lai, {Florence Y.} and Antonio Murgia and Bryony Eagle-Hemming and Sophia Sheikh and Tracy Kumar and Hardeep Aujla and Will Dott and Griffin, {Julian L.} and Murphy, {Gavin J.} and Wo{\'z}niak, {Marcin J.}",

note = "Funding Van Geest Foundation, Leicester NIHR Biomedical Research Centre, British Heart Foundation CH/12/1/29419, AA18/3/34220. Competing interests Mrs. Kumar, Prof. Murphy and Dr Wo{\'z}niak received a grant from Zimmer Biomet. Dr Murphy also received grants from Terumo and Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest.",

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AU - Adebayo, Adewale S.

AU - Roman, Marius

AU - Zakkar, Mustafa

AU - Yusoff, Syabira

AU - Gulston, Melanie

AU - Joel-David, Lathishia

AU - Anthony, Bony

AU - Lai, Florence Y.

AU - Murgia, Antonio

AU - Eagle-Hemming, Bryony

AU - Sheikh, Sophia

AU - Kumar, Tracy

AU - Aujla, Hardeep

AU - Dott, Will

AU - Griffin, Julian L.

AU - Murphy, Gavin J.

AU - Woźniak, Marcin J.

N1 - Funding Van Geest Foundation, Leicester NIHR Biomedical Research Centre, British Heart Foundation CH/12/1/29419, AA18/3/34220. Competing interests Mrs. Kumar, Prof. Murphy and Dr Woźniak received a grant from Zimmer Biomet. Dr Murphy also received grants from Terumo and Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest.

PY - 2022/1

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N2 - 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.

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

Abstract

Bibliographical note

Data Availability Statement

UN SDGs

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