%0 Journal Article %1 Metzner_2022 %A Metzner, Valentin %A Herzog, Gloria %A Heckel, Tobias %A Bischler, Thorsten %A Hasinger, Julia %A Otto, Christoph %A Fassnacht, Martin %A Geier, Andreas %A Seyfried, Florian %A Dischinger, Ulrich %D 2022 %I MDPI AG %J Journal of Clinical Medicine %K myown %N 3 %P 753 %R 10.3390/jcm11030753 %T Liraglutide + PYY3-36 Combination Therapy Mimics Effects of Roux-en-Y Bypass on Early NAFLD Whilst Lacking-Behind in Metabolic Improvements %U https://doi.org/10.3390%2Fjcm11030753 %V 11 %X 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. Keywords: liraglutide; GLP-1; peptide tyrosine tyrosine (PYY); peptide tyrosine tyrosine 3-36 (PYY3-36); RYGB; gastric bypass; obesity; NASH; NAFLD

@article{Metzner_2022, abstract = { 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. Keywords: liraglutide; GLP-1; peptide tyrosine tyrosine (PYY); peptide tyrosine tyrosine 3-36 (PYY3-36); RYGB; gastric bypass; obesity; NASH; NAFLD }, added-at = {2022-01-31T14:25:36.000+0100}, author = {Metzner, Valentin and Herzog, Gloria and Heckel, Tobias and Bischler, Thorsten and Hasinger, Julia and Otto, Christoph and Fassnacht, Martin and Geier, Andreas and Seyfried, Florian and Dischinger, Ulrich}, biburl = {https://www.bibsonomy.org/bibtex/231116280ad680f7e0e844f2810588cfd/cusysmed}, day = 30, description = {JCM | Free Full-Text | Liraglutide + PYY3-36 Combination Therapy Mimics Effects of Roux-en-Y Bypass on Early NAFLD Whilst Lacking-Behind in Metabolic Improvements | HTML}, doi = {10.3390/jcm11030753}, interhash = {f3016367c2e6c8f360002e37f926ea2b}, intrahash = {31116280ad680f7e0e844f2810588cfd}, journal = {Journal of Clinical Medicine}, keywords = {myown}, month = jan, number = 3, pages = 753, publisher = {MDPI AG}, timestamp = {2024-04-16T16:20:54.000+0200}, title = {Liraglutide + PYY3-36 Combination Therapy Mimics Effects of Roux-en-Y Bypass on Early NAFLD Whilst Lacking-Behind in Metabolic Improvements}, url = {https://doi.org/10.3390%2Fjcm11030753}, volume = 11, year = 2022 }