Liraglutide + PYY3-36 Combination Therapy Mimics Effects of Roux-en-Y Bypass on Early NAFLD Whilst Lacking-Behind in Metabolic Improvements

Autor: Valentin Metzner, Gloria Herzog, Tobias Heckel, Thorsten Bischler, Julia Hasinger, Christoph Otto, Martin Fassnacht, Andreas Geier, Florian Seyfried, Ulrich Dischinger
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Medicine, Vol 11, Iss 3, p 753 (2022)
Druh dokumentu: article
ISSN: 2077-0383
DOI: 10.3390/jcm11030753
Popis: 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 (PYY3-36) 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), PYY3-36 (0.1 mg/kg/day), liraglutide+PYY3-36, 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+PYY3-36 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+PYY3-36- 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+PYY3-36 partly mimics the positive effects of RYGB on weight reduction and on hepatic steatosis, while its effects on metabolic function lack behind RYGB.
Databáze: Directory of Open Access Journals
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