Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway
A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. T...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2019/1567095 |
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| author | Peng Yu Xi Xu Jing Zhang Xuan Xia Fen Xu Jianping Weng Xiaoyang Lai Yunfeng Shen |
| author_facet | Peng Yu Xi Xu Jing Zhang Xuan Xia Fen Xu Jianping Weng Xiaoyang Lai Yunfeng Shen |
| author_sort | Peng Yu |
| collection | DOAJ |
| description | A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway. |
| format | Article |
| id | doaj-art-0dbbe4b1161e44aba1d3623c23e10608 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-0dbbe4b1161e44aba1d3623c23e106082025-02-03T01:03:28ZengWileyInternational Journal of Endocrinology1687-83371687-83452019-01-01201910.1155/2019/15670951567095Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling PathwayPeng Yu0Xi Xu1Jing Zhang2Xuan Xia3Fen Xu4Jianping Weng5Xiaoyang Lai6Yunfeng Shen7Department of Endocrinology and Metabolism, Jiangxi Institute of Endocrine and Metabolic Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, Yichang, Hubei, ChinaDepartment of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, and Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, and Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, Jiangxi Institute of Endocrine and Metabolic Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Endocrinology and Metabolism, Jiangxi Institute of Endocrine and Metabolic Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaA glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway.http://dx.doi.org/10.1155/2019/1567095 |
| spellingShingle | Peng Yu Xi Xu Jing Zhang Xuan Xia Fen Xu Jianping Weng Xiaoyang Lai Yunfeng Shen Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway International Journal of Endocrinology |
| title | Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway |
| title_full | Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway |
| title_fullStr | Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway |
| title_full_unstemmed | Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway |
| title_short | Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway |
| title_sort | liraglutide attenuates nonalcoholic fatty liver disease through adjusting lipid metabolism via shp1 ampk signaling pathway |
| url | http://dx.doi.org/10.1155/2019/1567095 |
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