Liraglutide + PYY\(_{3-36}\) combination therapy mimics effects of Roux-en-Y bypass on early NAFLD whilst lacking-behind in metabolic improvements

Please always quote using this URN: urn:nbn:de:bvb:20-opus-255244
  • Background: Treatment options for NAFLD are still limited. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), has been shown to improve metabolic and histologic markers of NAFLD. Glucagon-like-peptide-1 (GLP-1) analogues lead to improvements in phase 2 clinical trials. We directly compared the effects of RYGB with a treatment using liraglutide and/or peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) in a rat model for early NAFLD. Methods: Obese male Wistar rats (high-fat diet (HFD)-induced) were randomized into the following treatmentBackground: Treatment options for NAFLD are still limited. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), has been shown to improve metabolic and histologic markers of NAFLD. Glucagon-like-peptide-1 (GLP-1) analogues lead to improvements in phase 2 clinical trials. We directly compared the effects of RYGB with a treatment using liraglutide and/or peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) in a rat model for early NAFLD. Methods: Obese male Wistar rats (high-fat diet (HFD)-induced) were randomized into the following treatment groups: RYGB, sham-operation (sham), liraglutide (0.4 mg/kg/day), PYY\(_{3-36}\) (0.1 mg/kg/day), liraglutide+PYY\(_{3-36}\), and saline. After an observation period of 4 weeks, liver samples were histologically evaluated, ELISAs and RNA sequencing + RT-qPCRs were performed. Results: RYGB and liraglutide+PYY\(_{3-36}\) induced a similar body weight loss and, compared to sham/saline, marked histological improvements with significantly less steatosis. However, only RYGB induced significant metabolic improvements (e.g., adiponectin/leptin ratio 18.8 ± 11.8 vs. 2.4 ± 1.2 in liraglutide+PYY\(_{3-36}\)- or 1.4 ± 0.9 in sham-treated rats). Furthermore, RNA sequencing revealed a high number of differentially regulated genes in RYGB treated animals only. Conclusions: The combination therapy of liraglutide+PYY\(_{3-36}\) partly mimics the positive effects of RYGB on weight reduction and on hepatic steatosis, while its effects on metabolic function lack behind RYGB.show moreshow less

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Metadaten
Author: Valentin Metzner, Gloria Herzog, Tobias Heckel, Thorsten Bischler, Julia Hasinger, Christoph Otto, Martin Fassnacht, Andreas Geier, Florian Seyfried, Ulrich Dischinger
URN:urn:nbn:de:bvb:20-opus-255244
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I)
Medizinische Fakultät / Pathologisches Institut
Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Medizinische Fakultät / Medizinische Klinik und Poliklinik I
Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):Journal of Clinical Medicine
ISSN:2077-0383
Year of Completion:2022
Volume:11
Issue:3
Article Number:753
Source:Journal of Clinical Medicine (2022) 11:3, 753. https://doi.org/10.3390/jcm11030753
DOI:https://doi.org/10.3390/jcm11030753
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:GLP-1; NAFLD; NASH; RYGB; gastric bypass; liraglutide; obesity; peptide tyrosine tyrosine (PYY); peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\))
Release Date:2022/09/27
Date of first Publication:2022/01/30
Open-Access-Publikationsfonds / Förderzeitraum 2022
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International