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Hoffmann Creator: Elsevier Producer: Acrobat Distiller 8.1.0 (Windows) CreationDate: Fri Dec 20 06:33:46 2019 CET ModDate: Fri Dec 20 06:34:43 2019 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 793.701 pts Page rot: 0 File size: 1432481 bytes Optimized: yes PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- APGLCI+AdvOTad521943 Type 1C WinAnsi yes yes no 812 0 APGLCJ+AdvP4C4E59 Type 1C WinAnsi yes yes no 815 0 APGLCK+AdvOT9d0303c0.B Type 1C WinAnsi yes yes no 817 0 APGLDL+AdvOT8e81dcaa Type 1C WinAnsi yes yes no 819 0 APGLDM+AdvPS44A44B Type 1C WinAnsi yes yes no 821 0 APGLDN+AdvOT8e81dcaa+fb Type 1C Custom yes yes yes 826 0 APGLDO+AdvPSSym Type 1C Custom yes yes no 828 0 APGLEO+AdvOTa4800bed.I Type 1C WinAnsi yes yes no 829 0 APGLEP+AdvP4C4E74 Type 1C Custom yes yes yes 835 0 APGLMO+ArialMT TrueType WinAnsi yes yes no 514 0 APGLNA+Arial-BoldMT TrueType WinAnsi yes yes no 512 0 APGLNC+Arial-ItalicMT TrueType WinAnsi yes yes no 519 0 APGMNO+Calibri-Italic TrueType WinAnsi yes yes no 522 0 APGMPO+Calibri CID TrueType Identity-H yes yes yes 515 0 APGNCO+AdvOT8e81dcaa+20 Type 1C WinAnsi yes yes no 516 0 APGODL+AdvPS3F4C13 Type 1C WinAnsi yes yes no 535 0 APGNLN+Calibri TrueType WinAnsi yes yes no 533 0 APGNLM+MyriadPro-Regular Type 1C WinAnsi yes yes no 532 0 APGOMI+Calibri-Bold CID TrueType Identity-H yes yes yes 543 0 APGOMJ+Calibri-Bold TrueType WinAnsi yes yes no 544 0 APHCDF+AdvPS3FDD77 Type 1C WinAnsi yes yes no 570 0 APHCDG+AdvOTa4800bed.I+20 Type 1C WinAnsi yes yes no 574 0 APHCEH+AdvP4C4E46 Type 1C WinAnsi yes yes no 577 0 APHCHH+AdvP4C4E51 Type 1C WinAnsi yes yes no 581 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-08-10 12:12:28 CEST RepresentationInformation: pmc_32029225.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-07-06 04:00:42 CEST Size: 1432481 Format: PDF Version: 1.7 Status: Well-Formed, but not valid SignatureMatches: PDF-hul ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - 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referenced object 'bib24' cannot be found Offset: 1401537 MIMEtype: application/pdf Profile: Linearized PDF PDFMetadata: Objects: 911 FreeObjects: 1 IncrementalUpdates: 1 DocumentCatalog: PageLayout: SinglePage PageMode: UseOutlines Outlines: Item: Title: BMP4 gene therapy enhances insulin sensitivity but not adipose tissue browning in obese mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Children: Item: Title: 1. Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: 2. Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Children: Item: Title: 2.1. Increased hepatic and serum BMP4 levels following AAV8 BMP4 injections, but not in peripheral tissues Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: 2.2. AAV8 BMP4 gene therapy in obese mice does not induce weight loss or browning of WAT Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: 2.3. Reduced BMP signaling in subcutaneous adipose tissue but not in skeletal muscle or in liver Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: 2.4. Improved insulin sensitivity and glucose homeostasis in obese AAV8 BMP4 mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: 2.5. Tissue glucose uptake Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: 2.6. BMP4 also enhances hepatic insulin signaling and reduces hepatic gluconeogenic enzymes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: 3. Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: 4. Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: 5. Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Children: Item: Title: 5.1. Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Item: Title: 5.2. Recombinant adeno-associated viral vectors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: 5.3. GTT, ITT, and PTT Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: 5.4. Oxygen consumption and activity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Item: Title: 5.5. Glucose uptake Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Children: Item: Title: 5.5.1. In vivo protocol Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Item: Title: 5.5.2. Measurement of plasma and tissue 14C-2DG activity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Item: Title: 5.5.3. Calculation of tissue-specific glucose clearance (Kg’) and utilization (Rg’) indices Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b Item: Title: 5.6. In vivo insulin stimulation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b Item: Title: 5.7. Serum chemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31 Item: Title: 5.8. Liver triglyceride content Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@b7dd107 Item: Title: 5.9. Insulin stimulation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@42eca56e Children: Item: Title: 5.9.1. Isolated adipocytes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@52f759d7 Item: Title: 5.9.2. Human hepatocyte cell line (IHH) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7cbd213e Item: Title: 5.10. Immunoprecipitation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@192d3247 Children: Item: Title: 5.10.1. Immunoprecipitation of BMP4 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3ecd23d9 Item: Title: 5.10.2. Immunoprecipitation and acetylation analysis of PGC1-a Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@569cfc36 Item: Title: 5.11. BMP reporter assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@43bd930a Item: Title: 5.12. Immunoblotting Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@33723e30 Item: Title: 5.13. Measurement of islet size Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@64f6106c Item: Title: 5.14. Gene expression analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@553a3d88 Item: Title: 5.15. Statistical calculations and figures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a30d1e6 Item: Title: Author contributions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5891e32e Item: Title: Funding Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@cb0ed20 Item: Title: Acknowledgements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8e24743 Item: Title: Conflict of interest Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74a10858 Item: Title: Appendix A. Supplementary data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@23fe1d71 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@28ac3dc3 Info: Title: BMP4 gene therapy enhances insulin sensitivity but not adipose tissue browning in obese mice Author: Jenny M. 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Hoffmann John R. Grünberg Ann Hammarstedt Tobias Kroon Thomas U. Greiner Stefanie Maurer Ivet Elias Vilborg Palsdottir Fatima Bosch Jeremie Boucher Shahram Hedjazifar Ulf Smith Obesity Gene therapy Insulin sensitivity Adipose tissue Skeletal muscle Liver Molecular Metabolism, 32 (2020) 15-26. doi:10.1016/j.molmet.2019.11.016 Elsevier GmbH journal Molecular Metabolism © 2019 The Author(s). Published by Elsevier GmbH. 2212-8778 32 February 2020 15-26 15 26 10.1016/j.molmet.2019.11.016 https://doi.org/10.1016/j.molmet.2019.11.016 2010-04-23 true 10.1016/j.molmet.2019.11.016 elsevier.com sciencedirect.com VoR 6.5 10.1016/j.molmet.2019.11.016 noindex 2010-04-23 true sciencedirect.com elsevier.com Elsevier 2019-12-20T11:03:46+05:30 2019-12-20T11:04:43+05:30 2019-12-20T11:04:43+05:30 True Acrobat Distiller 8.1.0 (Windows) uuid:3ae9307d-d878-4146-8cd9-f868b2ea1eaf uuid:db0a76b7-5cdc-4be0-9a40-159f23698681 http://creativecommons.org/licenses/by-nc-nd/4.0/ Pages: Page: Label: 15 Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 119, 606, 123, 615 Destination: 745 Annotation: Subtype: Link Rect: 197, 606, 201, 615 Destination: 745 Annotation: Subtype: Link Rect: 277, 606, 281, 615 Destination: 745 Annotation: Subtype: Link Rect: 338, 606, 342, 615 Destination: 745 Annotation: Subtype: Link Rect: 420, 606, 423, 615 Destination: 745 Annotation: Subtype: Link Rect: 105, 595, 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