38c6d76e3d00775b15fc40315ffc9adf 271458.pdf 1334fb222d0d8b61bfc9ef4830ce1e1431927f8d 271458.pdf b9d4ec6b2208eaa1e3da6fc61c4fe4314dc7806deba42e30946144dd96a45565 271458.pdf Title: Divergent Effects of Glycemic Control and Bariatric Surgery on Circulating Concentrations of TMAO in Newly Diagnosed T2D Patients and Morbidly Obese Subject: High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, -butyrobetaine (BB), in newly diagnosed T2D patients and morbidly obese subjects following a within-subject design. Based on HbA1c concentrations, T2D patients achieved glycemic control. However, the plasma TMAO and BB concentrations were significantly increased, without changes in estimated glomerular filtration rate. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma BB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Considering these results, an additional experiment was carried out in male C57BL/6J mice fed a Western-type diet for twelve weeks. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and BB concentrations in these genetically defined mice strains. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients. Keywords: -butyrobetaine; glycemic control; liquid chromatography–mass spectrometry; obesity; trimethylamine N-oxide; type 2 diabetes Author: Marina Canyelles, Antonio Pérez, Alexandra Junza, Inka Miñambres, Oscar Yanes, Helena Sardà, Noemí Rotllan, Josep Julve, José Luis Sánchez-Quesada, Mireia Tondo, Joan Carles Escolà-Gil and Francisco Blanco-Vaca Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Nov 21 12:41:32 2022 CET ModDate: Mon Nov 21 12:55:20 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 899124 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OHKNFJ+VnURWPalladioL Type 1 Custom yes yes no 10 0 MDJLZU+EURM10 Type 1 Builtin yes yes no 15 0 DSHKRD+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 GRGVBB+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 DGVWVQ+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 VJNASK+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 BXZUUH+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 72 0 XCPSDD+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 85 0 MRDEFZ+PalatinoLinotype-Italic TrueType WinAnsi yes yes yes 93 0 KGBSDD+PalatinoLinotype-Roman TrueType WinAnsi yes yes yes 97 0 NARPTX+PalatinoLinotype-Bold TrueType WinAnsi yes yes yes 101 0 BYOLHV+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes yes 105 0 AKXRSZ+EURB10 Type 1 Builtin yes yes no 115 0 UWJUYN+CMSY10 Type 1 Builtin yes yes no 119 0 XCPSDD+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 128 0 VMSLBH+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 136 0 MRDEFZ+PalatinoLinotype-Italic TrueType WinAnsi yes yes yes 144 0 KGBSDD+PalatinoLinotype-Roman TrueType WinAnsi yes yes yes 148 0 NARPTX+PalatinoLinotype-Bold TrueType WinAnsi yes yes yes 152 0 XCPSDD+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 167 0 MRDEFZ+PalatinoLinotype-Italic TrueType WinAnsi yes yes yes 175 0 KGBSDD+PalatinoLinotype-Roman TrueType WinAnsi yes yes yes 179 0 NARPTX+PalatinoLinotype-Bold TrueType WinAnsi yes yes yes 183 0 GEWEQC+PazoMath-Italic Type 1 Builtin yes yes no 195 0 BBETNX+PazoMath Type 1 Builtin yes yes no 208 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-02-14 02:31:10 CET RepresentationInformation: 271458.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-02-13 12:59:53 CET Size: 899124 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 368 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Cohort Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Gut-Derived Metabolites in T2D and Obese Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Mice Experiments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Subjects and Biochemical Parameters Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Mice, Diet, and the Homeostatic Model Assessment of Insulin Resistance(HOMA-IR) Determinations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Plasma TMAO and BB Quantification Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Statistics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Info: Title: Divergent Effects of Glycemic Control and Bariatric Surgery on Circulating Concentrations of TMAO in Newly Diagnosed T2D Patients and Morbidly Obese Author: Marina Canyelles, Antonio Pérez, Alexandra Junza, Inka Miñambres, Oscar Yanes, Helena Sardà, Noemí Rotllan, Josep Julve, José Luis Sánchez-Quesada, Mireia Tondo, Joan Carles Escolà-Gil and Francisco Blanco-Vaca Subject: High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, -butyrobetaine (BB), in newly diagnosed T2D patients and morbidly obese subjects following a within-subject design. Based on HbA1c concentrations, T2D patients achieved glycemic control. However, the plasma TMAO and BB concentrations were significantly increased, without changes in estimated glomerular filtration rate. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma BB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Considering these results, an additional experiment was carried out in male C57BL/6J mice fed a Western-type diet for twelve weeks. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and BB concentrations in these genetically defined mice strains. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients. 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