Liraglutide reduces hepatic glucolipotoxicity‑induced liver cell apoptosis through NRF2 signaling in Zucker diabetic fatty rats

Guo,Jun; Li,Cai; Yang,Chunxiao; Li,Bing; Wei,Jie; Lin,Yajun; Ye,Peng; Hu,Gang; Li,Jian

doi:10.3892/mmr.2018.8919

Liraglutide reduces hepatic glucolipotoxicity‑induced liver cell apoptosis through NRF2 signaling in Zucker diabetic fatty rats

Authors:
- Jun Guo
- Cai Li
- Chunxiao Yang
- Bing Li
- Jie Wei
- Yajun Lin
- Peng Ye
- Gang Hu
- Jian Li
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Affiliations: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China, Department of Encephalopathy, Medical Department of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
Published online on: April 23, 2018 https://doi.org/10.3892/mmr.2018.8919
Pages: 8316-8324
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The primary aim of the present study was to evaluate the effects of liraglutide on glucolipotoxicity‑induced liver cell apoptosis and the underlying mechanisms in Zucker diabetic fatty (ZDF) rats. The results revealed that liraglutide significantly decreased the body weight, hyperglycemia and hyperlipidemia of ZDF rats relative to those of Zucker lean (ZL) rats (P<0.05). Furthermore, the reduced liver cell apoptosis was observed in the ZDF rats following 6 weeks of liraglutide therapy. These data validated the beneficial effects of liraglutide on diabetic and obese ZDF rats. In addition, novel data was obtained that demonstrated that liraglutide treatment increased the expression of the antioxidant transcription factor nuclear factor‑erythroid 2‑related factor 2 (NRF2), as well as the transcription of downstream target genes, including nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 and heme oxygenase‑1 (P<0.05). Additionally, serum and hepatic GSH and SOD levels increased following liraglutide therapy (P<0.05). Hence, it was proposed that liraglutide may enhance the antioxidant activity of liver cells by activating the NRF2 signaling pathway, thereby reducing liver cell apoptosis induced by glucolipotoxicity in ZDF rats, which may shed light on the application of liraglutide in the treatment of diabetes‑ and obesity‑induced liver injury.

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