Diabetologie und Stoffwechsel 2021; 16(S 01): S37
DOI: 10.1055/s-0041-1727388
04. Grundlagenforschung Adipositas/Metabolisches Syndrom

Effects of liraglutide + / - PYY3-36 vs. Roux-en-Y gastric bypass on non-alcoholic fatty liver disease

U Dischinger
1   University Hospital, University of Würzburg, Department of Internal Medicine, Division of Endocrinology and Diabetes, Würzburg, Germany
,
V Metzner
1   University Hospital, University of Würzburg, Department of Internal Medicine, Division of Endocrinology and Diabetes, Würzburg, Germany
,
G Herzog
2   University of Würzburg, Germany, Institute of Pathology, Würzburg, Germany
,
M Hankir
3   University Hospital, University of Würzburg, Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, Würzburg, Germany
,
F Seyfried
3   University Hospital, University of Würzburg, Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, Würzburg, Germany
,
M Fassnacht
1   University Hospital, University of Würzburg, Department of Internal Medicine, Division of Endocrinology and Diabetes, Würzburg, Germany
,
A Geier
4   University Hospital, University of Würzburg, Germany, Department of Internal Medicine, Division of Hepatology, Würzburg, Germany
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Background Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in obese individuals. Roux-en-Y gastric bypass (RYGB) is highly effective in terms of body weight loss, but also improves histologic and metabolic markers of NAFLD. Regarding conservative treatment options, liraglutide also confers histological improvement. We directly compared the effects of RYGB and a treatment with liraglutide and peptide tyrosine tyrosine 3-36 (PYY3-36) on NAFLD.

Methods High-fat diet (HFD)-induced obese male Wistar rats (n = 58; mean weight 504g) were randomized into 6 treatment groups: RYGB, sham-operation, liraglutide (0.4mg/kg/day), PYY3-36 (0.1mg/kg/day), PYY3-36+liraglutide and saline. Animals had free access to high- and low-fat diet. Food preference and intake was monitored. After an observation period of 4 weeks, liver samples were histologically evaluated.

Results RYGB and PYY3-36+liraglutide treatment led to a similar and plateaued weight loss, reduced overall food intake and (less pronounced) high-fat preference compared to controls. Only RYBG induced marked histological improvements with significantly less microvesicular steatosis compared to sham-operation (p ≤ 0.05). Although less effective regarding food intake / body weight, liraglutide monotherapy revealed similar beneficial effects on the liver as liraglutide+PYY3-36, which had both partial antisteatotic effects.

Conclusions PYY3-36+liraglutide combination therapy mimics the positive effects of RYGB on weight reduction, but only partially on hepatic steatosis. Regarding histologic phenotype, liraglutide and PYY3-36+liraglutide are equally effective indicating a leading effect of GLP-1 signaling. This underlines the potential of GLP-1 agonists in the treatment of obesity and related NAFLD, but indicates that an extended treatment duration might be necessary compared to early effects of RYGB.



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Artikel online veröffentlicht:
06. Mai 2021

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