Effect of Saxagliptin, a Dipeptidyl Peptidase 4 Inhibitor, on Non-Alcoholic Fatty Liver Disease

Lin Chen,1,* Xiujuan Zhang,2,* Li Zhang,3 Dongmei Zheng2 1Department of Breast and Thyroid Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Endocrinology, Shandong Provincial Hospital Affili...

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Autores principales:	Chen L, Zhang X, Zhang L, Zheng D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	dipeptidyl peptidase 4 inhibitor non-alcoholic fatty liver disease inflammation insulin resistance Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/0a588079ca504ff588952d8b77168fb7
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spelling	oai:doaj.org-article:0a588079ca504ff588952d8b77168fb72021-12-02T12:22:21ZEffect of Saxagliptin, a Dipeptidyl Peptidase 4 Inhibitor, on Non-Alcoholic Fatty Liver Disease1178-7007https://doaj.org/article/0a588079ca504ff588952d8b77168fb72020-10-01T00:00:00Zhttps://www.dovepress.com/effect-of-saxagliptin-a-dipeptidyl-peptidase-4-inhibitor-on-non-alcoho-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Lin Chen,1,* Xiujuan Zhang,2,* Li Zhang,3 Dongmei Zheng2 1Department of Breast and Thyroid Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongmei ZhengDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, People’s Republic of ChinaTel + 86 531 68776375Email zhengdongmei1971@163.comBackground and Aim: Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum of chronic liver disease characterized by aberrant accumulation of triglycerides (TG) in hepatocytes without excessive alcohol consumption. Hepatic lipotoxicity derived from overaccumulation of free fatty acids is considered as one of the typical hallmarks of NAFLD. Insulin resistance (IR) and chronic inflammation are widely recognized as the key etiological factors associated with NAFLD. Dipeptidyl peptidase 4 inhibitor (DPP4i) is a novel pharmacological agent extensively applied in the treatment of Type 2 Diabetes Mellitus (T2DM) for decades which also have a liver protective effect.Methods: In order to invest the therapeutic efficiency and underlying mechanism of DPP4i saxagliptin, we used high-fat diet (HFD) and streptozotocin-induced NAFLD treated with saxagliptin. Biochemical, histomorphological, genetic and protein expression of related pathways were investigated.Results: Fasting blood glucose (FBG), TG, total cholesterol (TC), and low-density lipoprotein cholesterin significantly increased in NAFLD group, which also exhibited severe steatosis. Other remarkable findings were hyperinsulinemia, increased DPP4, PTP-1B and TNF-α level and decreased GLP-1, ACOX-1, CPT-1A expression, concomitant with liver DPP4 expression enhancement and serum DPP4 elevation. These undesirable consequences were alleviated by saxagliptin to a certain degree.Conclusion: DPP4i saxagliptin improves NAFLD by ameliorating IR, inflammation, downregulation of hepatic DPP4 and sDPP4, as well as subsequent steatosis. The elevation of hepatic DPP4 and sDPP4 and succedent post-treatment decrease suggested that DPP4 may involve in the development of NAFLD. The anti-lipotoxic effect of DPP4i may involve the activation of CPT1A and ACOX1 related β-oxidation signaling pathway suppression of TNF-α mediated inflammatory and PTP-1B. The results covered in this article showed that saxagliptin affects many aspects of the pathological characteristics of NAFLD, suggesting that DPP4i saxagliptin may offer a novel therapeutic option for NAFLD.Keywords: dipeptidyl peptidase 4 inhibitor DPP4i, non-alcoholic fatty liver disease NAFLD, inflammation, insulin resistance IRChen LZhang XZhang LZheng DDove Medical Pressarticledipeptidyl peptidase 4 inhibitornon-alcoholic fatty liver diseaseinflammationinsulin resistanceSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 3507-3518 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	dipeptidyl peptidase 4 inhibitor non-alcoholic fatty liver disease inflammation insulin resistance Specialties of internal medicine RC581-951
spellingShingle	dipeptidyl peptidase 4 inhibitor non-alcoholic fatty liver disease inflammation insulin resistance Specialties of internal medicine RC581-951 Chen L Zhang X Zhang L Zheng D Effect of Saxagliptin, a Dipeptidyl Peptidase 4 Inhibitor, on Non-Alcoholic Fatty Liver Disease
description	Lin Chen,1,* Xiujuan Zhang,2,* Li Zhang,3 Dongmei Zheng2 1Department of Breast and Thyroid Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongmei ZhengDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, People’s Republic of ChinaTel + 86 531 68776375Email zhengdongmei1971@163.comBackground and Aim: Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum of chronic liver disease characterized by aberrant accumulation of triglycerides (TG) in hepatocytes without excessive alcohol consumption. Hepatic lipotoxicity derived from overaccumulation of free fatty acids is considered as one of the typical hallmarks of NAFLD. Insulin resistance (IR) and chronic inflammation are widely recognized as the key etiological factors associated with NAFLD. Dipeptidyl peptidase 4 inhibitor (DPP4i) is a novel pharmacological agent extensively applied in the treatment of Type 2 Diabetes Mellitus (T2DM) for decades which also have a liver protective effect.Methods: In order to invest the therapeutic efficiency and underlying mechanism of DPP4i saxagliptin, we used high-fat diet (HFD) and streptozotocin-induced NAFLD treated with saxagliptin. Biochemical, histomorphological, genetic and protein expression of related pathways were investigated.Results: Fasting blood glucose (FBG), TG, total cholesterol (TC), and low-density lipoprotein cholesterin significantly increased in NAFLD group, which also exhibited severe steatosis. Other remarkable findings were hyperinsulinemia, increased DPP4, PTP-1B and TNF-α level and decreased GLP-1, ACOX-1, CPT-1A expression, concomitant with liver DPP4 expression enhancement and serum DPP4 elevation. These undesirable consequences were alleviated by saxagliptin to a certain degree.Conclusion: DPP4i saxagliptin improves NAFLD by ameliorating IR, inflammation, downregulation of hepatic DPP4 and sDPP4, as well as subsequent steatosis. The elevation of hepatic DPP4 and sDPP4 and succedent post-treatment decrease suggested that DPP4 may involve in the development of NAFLD. The anti-lipotoxic effect of DPP4i may involve the activation of CPT1A and ACOX1 related β-oxidation signaling pathway suppression of TNF-α mediated inflammatory and PTP-1B. The results covered in this article showed that saxagliptin affects many aspects of the pathological characteristics of NAFLD, suggesting that DPP4i saxagliptin may offer a novel therapeutic option for NAFLD.Keywords: dipeptidyl peptidase 4 inhibitor DPP4i, non-alcoholic fatty liver disease NAFLD, inflammation, insulin resistance IR
format	article
author	Chen L Zhang X Zhang L Zheng D
author_facet	Chen L Zhang X Zhang L Zheng D
author_sort	Chen L
title	Effect of Saxagliptin, a Dipeptidyl Peptidase 4 Inhibitor, on Non-Alcoholic Fatty Liver Disease
title_short	Effect of Saxagliptin, a Dipeptidyl Peptidase 4 Inhibitor, on Non-Alcoholic Fatty Liver Disease
title_full	Effect of Saxagliptin, a Dipeptidyl Peptidase 4 Inhibitor, on Non-Alcoholic Fatty Liver Disease
title_fullStr	Effect of Saxagliptin, a Dipeptidyl Peptidase 4 Inhibitor, on Non-Alcoholic Fatty Liver Disease
title_full_unstemmed	Effect of Saxagliptin, a Dipeptidyl Peptidase 4 Inhibitor, on Non-Alcoholic Fatty Liver Disease
title_sort	effect of saxagliptin, a dipeptidyl peptidase 4 inhibitor, on non-alcoholic fatty liver disease
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/0a588079ca504ff588952d8b77168fb7
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Effect of Saxagliptin, a Dipeptidyl Peptidase 4 Inhibitor, on Non-Alcoholic Fatty Liver Disease

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