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

Journal of Clinical Medicine

Thorsten Bischler¹  Tobias Heckel¹  Christoph Otto²  Florian Seyfried²  Julia Hasinger³  Valentin Metzner³  Martin Fassnacht³  Ulrich Dischinger³  Andreas Geier⁴  Gloria Herzog⁵ 

[1] Core Unit Systems Medicine, University of Würzburg, 97080 Würzburg, Germany;Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital Würzburg, 97080 Würzburg, Germany;Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital Würzburg, 97080 Würzburg, Germany;Division of Hepatology, Department of Internal Medicine, University Hospital Würzburg, 97080 Würzburg, Germany;Institute of Pathology, University of Würzburg, 97080 Würzburg, Germany;

关键词: liraglutide;    GLP-1;    peptide tyrosine tyrosine (PYY);    peptide tyrosine tyrosine 3-36 (PYY_3-36);    RYGB;    gastric bypass;   

DOI  :  10.3390/jcm11030753

来源: DOAJ

【 摘 要 】

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 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.

【 授权许可】

Unknown