Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway

Pijian Yang1,*, Yuzhen Liang2,*, Yunchen Luo,2 Zhengming Li,2 Yumei Wen,1 Jing Shen,1 Ruwen Li,1 Hua Zheng,3 Harvest F Gu4,*, Ning Xia1,*1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 2De...

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Autores principales:	Yang P, Liang Y, Luo Y, Li Z, Wen Y, Shen J, Li R, Zheng H, Gu HF, Xia N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Glucagon like peptide 1 Liraglutide Nonalcoholic fatty liver disease Insulin resistance Insulin signaling Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/46cd31beb13d45f5b0ecb6789895100c
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spelling	oai:doaj.org-article:46cd31beb13d45f5b0ecb6789895100c2021-12-02T03:08:22ZLiraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway1178-7007https://doaj.org/article/46cd31beb13d45f5b0ecb6789895100c2019-07-01T00:00:00Zhttps://www.dovepress.com/liraglutide-ameliorates-nonalcoholic-fatty-liver-disease-in-diabetic-m-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Pijian Yang1,, Yuzhen Liang2,, Yunchen Luo,2 Zhengming Li,2 Yumei Wen,1 Jing Shen,1 Ruwen Li,1 Hua Zheng,3 Harvest F Gu4,, Ning Xia1,1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 3Life Sciences Institute, Guangxi Medical University, Nanning 530021, People’s Republic of China; 4Center for Pathophysiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009 People’s Republic of China*These authors contributed equally to this workPurpose: High prevalence of nonalcoholic fatty liver disease (NAFLD) among patients with type 2 diabetes has implicated the role of hepatic insulin resistance (IR) in the diseases. To better understand the underlying mechanism, we have evaluated the pathophysiological effects of Liraglutide on NAFLD via the insulin signaling pathway.Patients and methods: A 2×2 factorial experiment was designed. High-fat diet (HFD)-induced NAFLD mice with diabetes were treated with Liraglutide for 10 weeks, while the control mice were saline-treated. Hepatic expressions of InsR, IGF-1R, IRS2, PI3K and Akt at mRNA and protein levels were analyzed with RT-PCR and Western blotting. Hematoxylin and eosin staining, Oil Red O staining and electron microscopy were used to visualize triglyceride accumulation in liver.Results: Liraglutide significantly decreased body weight, fasting blood glucose levels and HOMA-IR scores in HFD mice. Compared with the control mice fed with chow diet, hepatic expressions of InsR, IRS2, PI3K and Akt at both mRNA and protein levels in HFD mice were significantly reduced, but upregulated after Liraglutide treatment. Furthermore, Liraglutide treatment was found to improve hepatic steatosis.Conclusion: The current study thereby provides evidence that Liraglutide ameliorates NAFLD and improves hepatic steatosis mainly by upregulation of the IRS2/PI3K/Akt signaling mediators.Keywords: glucagon like peptide 1, Liraglutide, nonalcoholic fatty liver disease, insulin resistance, insulin signalingYang PLiang YLuo YLi ZWen YShen JLi RZheng HGu HFXia NDove Medical PressarticleGlucagon like peptide 1LiraglutideNonalcoholic fatty liver diseaseInsulin resistanceInsulin signalingSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 1013-1021 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Glucagon like peptide 1 Liraglutide Nonalcoholic fatty liver disease Insulin resistance Insulin signaling Specialties of internal medicine RC581-951
spellingShingle	Glucagon like peptide 1 Liraglutide Nonalcoholic fatty liver disease Insulin resistance Insulin signaling Specialties of internal medicine RC581-951 Yang P Liang Y Luo Y Li Z Wen Y Shen J Li R Zheng H Gu HF Xia N Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway
description	Pijian Yang1,, Yuzhen Liang2,, Yunchen Luo,2 Zhengming Li,2 Yumei Wen,1 Jing Shen,1 Ruwen Li,1 Hua Zheng,3 Harvest F Gu4,, Ning Xia1,1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 3Life Sciences Institute, Guangxi Medical University, Nanning 530021, People’s Republic of China; 4Center for Pathophysiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009 People’s Republic of China*These authors contributed equally to this workPurpose: High prevalence of nonalcoholic fatty liver disease (NAFLD) among patients with type 2 diabetes has implicated the role of hepatic insulin resistance (IR) in the diseases. To better understand the underlying mechanism, we have evaluated the pathophysiological effects of Liraglutide on NAFLD via the insulin signaling pathway.Patients and methods: A 2×2 factorial experiment was designed. High-fat diet (HFD)-induced NAFLD mice with diabetes were treated with Liraglutide for 10 weeks, while the control mice were saline-treated. Hepatic expressions of InsR, IGF-1R, IRS2, PI3K and Akt at mRNA and protein levels were analyzed with RT-PCR and Western blotting. Hematoxylin and eosin staining, Oil Red O staining and electron microscopy were used to visualize triglyceride accumulation in liver.Results: Liraglutide significantly decreased body weight, fasting blood glucose levels and HOMA-IR scores in HFD mice. Compared with the control mice fed with chow diet, hepatic expressions of InsR, IRS2, PI3K and Akt at both mRNA and protein levels in HFD mice were significantly reduced, but upregulated after Liraglutide treatment. Furthermore, Liraglutide treatment was found to improve hepatic steatosis.Conclusion: The current study thereby provides evidence that Liraglutide ameliorates NAFLD and improves hepatic steatosis mainly by upregulation of the IRS2/PI3K/Akt signaling mediators.Keywords: glucagon like peptide 1, Liraglutide, nonalcoholic fatty liver disease, insulin resistance, insulin signaling
format	article
author	Yang P Liang Y Luo Y Li Z Wen Y Shen J Li R Zheng H Gu HF Xia N
author_facet	Yang P Liang Y Luo Y Li Z Wen Y Shen J Li R Zheng H Gu HF Xia N
author_sort	Yang P
title	Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway
title_short	Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway
title_full	Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway
title_fullStr	Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway
title_full_unstemmed	Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway
title_sort	liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the irs2/pi3k/akt signaling pathway
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/46cd31beb13d45f5b0ecb6789895100c
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Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway

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