GSE192425
Liraglutide + PYY3-36 combination therapy mimics effects of Roux-en-Y bypass on early NAFLD whilst lacking-behind in metabolic improvements.
Background: Non-alcoholic fatty liver disease (NAFLD) is common in the general population. Treatment options for NAFLD are very limited, GLP-1 analogues, however, seem to be effective. Roux-en-Y gastric bypass (RYGB) is highly effective in terms of body weight loss and improves histologic and metabolic markers of NAFLD. We directly compared the effects of RYGB and a treatment with liraglutide and/or peptide tyrosine tyrosine 3-36 (PYY3-36) on early NAFLD. Methods: High-fat diet (HFD)-induced obese male Wistar rats were randomized into 6 treatment groups: RYGB, sham-operation (Sham), liraglutide (0.4mg/kg/day), PYY3-36 (0.1mg/kg/day), li-raglutide+PYY3-36 and saline. Following intervention and after an observation period of 4 weeks liver samples were histologically evaluated, ELISAs and RT-qPCRs +RNA sequencing were per-formed. Results: RYGB and liraglutide+PYY3-36 induced a similar body weight loss and marked histological improvements with significantly less steatosis compared to sham/saline. However, only RYGB induced significant metabolic improvements and mRNA expression changes. Con-clusions: liraglutide+PYY3-36 combination therapy mimics the positive effects of RYGB on weight reduction and on hepatic steatosis, while its effects on insulin resistance and adipose tissue dys-function (adiponectin/leptin ratio) lack behind RYGB. Overall design: Examination of changes of mRNA in different treatment groupts in livers of male Wistar rats