TY  - JOUR
A1  - Metzner, Valentin
A1  - Herzog, Gloria
A1  - Heckel, Tobias
A1  - Bischler, Thorsten
A1  - Hasinger, Julia
A1  - Otto, Christoph
A1  - Fassnacht, Martin
A1  - Geier, Andreas
A1  - Seyfried, Florian
A1  - Dischinger, Ulrich
T1  - Liraglutide + PYY\(_{3-36}\) combination therapy mimics effects of Roux-en-Y bypass on early NAFLD whilst lacking-behind in metabolic improvements
JF  - Journal of Clinical Medicine
N2  - 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.
KW  - liraglutide
KW  - GLP-1
KW  - peptide tyrosine tyrosine (PYY)
KW  - peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\))
KW  - RYGB
KW  - gastric bypass
KW  - obesity
KW  - NASH
KW  - NAFLD
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-255244
SN  - 2077-0383
VL  - 11
IS  - 3
ER  -