Dysregulation of DPP4 Is Associated with the AMPK/JAK2/STAT3 Pathway in Adipocytes Under Insulin Resistance Status and Liraglutide Intervention

Fangxiao Cheng,1 Geheng Yuan,1 Jiao He,2 Yimin Shao,1 Junqing Zhang,1 Xiaohui Guo1 1Department of Endocrinology, Peking University First Hospital, Beijing 100034, People’s Republic of China; 2Department of Endocrinology, Baoding First Central Hospital, Baoding 071000, Hebei Province, Peopl...

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Autores principales:	Cheng F, Yuan G, He J, Shao Y, Zhang J, Guo X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	obesity adipocyte dpp4 ampk jak2/stat3 liraglutide insulin resistance Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/eab2571805934175a738ba9512894384
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spelling	oai:doaj.org-article:eab2571805934175a738ba95128943842021-12-02T03:19:59ZDysregulation of DPP4 Is Associated with the AMPK/JAK2/STAT3 Pathway in Adipocytes Under Insulin Resistance Status and Liraglutide Intervention1178-7007https://doaj.org/article/eab2571805934175a738ba95128943842019-12-01T00:00:00Zhttps://www.dovepress.com/dysregulation-of-dpp4-is-associated-with-the-ampkjak2stat3-pathway-in--peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Fangxiao Cheng,1 Geheng Yuan,1 Jiao He,2 Yimin Shao,1 Junqing Zhang,1 Xiaohui Guo1 1Department of Endocrinology, Peking University First Hospital, Beijing 100034, People’s Republic of China; 2Department of Endocrinology, Baoding First Central Hospital, Baoding 071000, Hebei Province, People’s Republic of ChinaCorrespondence: Geheng Yuan; Xiaohui GuoDepartment of Endocrinology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, People’s Republic of ChinaTel\|Fax +86 010 83575103Email 139197109@qq.com; bdyyguoxiaohui@sina.comPurpose: Dipeptidyl peptidase 4 (DPP4) is one of the newly identified adipokines, which acts as paracrine in adipose tissue and as endocrine hormones in the liver, muscles and central nervous system. Expression of DPP4 was significantly upregulated in obese patients upon insulin resistance (IR) conditions, but the mechanism underlying the dysregulation of DPP4 remains unclear. This study aimed to investigate the DPP4 expression in adipose tissue and adipocytes under IR conditions or with liraglutide intervention, and explore the potential molecular mechanisms.Methods: Obesity-associated IR animal and cell models were, respectively, constructed by using high-fat diet and palmitic acid (PA) stimulation. Expression of DPP4 in adipose tissues and adipocytes was estimated by quantitative real-time RT-PCR and Western-blot. Effects of the AMPK/JAK2/STAT3 pathway on DPP4 were examined by regulating the activity of AMPK and the JAK2/STAT signaling. The therapeutic efficacy of liraglutide in the IR models was evaluated, and its regulatory effects on DPP4 expression and the underlying molecular mechanisms were explored.Results: The expression of DPP4 was markedly upregulated in both the animal and cell IR models. In the adipocyte, DPP4 expression was found to be suppressed by the activation of AMPK, and this inhibition effect was mediated by the JAK2/STAT3 signaling. Moreover, liraglutide could alleviate the obesity-induced IR, and led to the downregulation of DPP4 in IR animal and cell models. Liraglutide intervention resulted in the activation of AMPK and deactivation of the JAK2/STAT3 signaling in the adipocytes.Conclusion: Taken together, the expression of DPP4 is upregulated in adipose tissues and adipocytes upon IR conditions, but is reduced after liraglutide intervention. The dysregulation of DPP4 in the adipocytes may be performed by the AMPK/JAK2/STAT3 pathway.Keywords: obesity, adipocyte, DPP4, AMPK, JAK2/STAT3, liraglutide, insulin resistance  Cheng FYuan GHe JShao YZhang JGuo XDove Medical Pressarticleobesityadipocytedpp4ampkjak2/stat3liraglutideinsulin resistanceSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 2635-2644 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	obesity adipocyte dpp4 ampk jak2/stat3 liraglutide insulin resistance Specialties of internal medicine RC581-951
spellingShingle	obesity adipocyte dpp4 ampk jak2/stat3 liraglutide insulin resistance Specialties of internal medicine RC581-951 Cheng F Yuan G He J Shao Y Zhang J Guo X Dysregulation of DPP4 Is Associated with the AMPK/JAK2/STAT3 Pathway in Adipocytes Under Insulin Resistance Status and Liraglutide Intervention
description	Fangxiao Cheng,1 Geheng Yuan,1 Jiao He,2 Yimin Shao,1 Junqing Zhang,1 Xiaohui Guo1 1Department of Endocrinology, Peking University First Hospital, Beijing 100034, People’s Republic of China; 2Department of Endocrinology, Baoding First Central Hospital, Baoding 071000, Hebei Province, People’s Republic of ChinaCorrespondence: Geheng Yuan; Xiaohui GuoDepartment of Endocrinology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, People’s Republic of ChinaTel\|Fax +86 010 83575103Email 139197109@qq.com; bdyyguoxiaohui@sina.comPurpose: Dipeptidyl peptidase 4 (DPP4) is one of the newly identified adipokines, which acts as paracrine in adipose tissue and as endocrine hormones in the liver, muscles and central nervous system. Expression of DPP4 was significantly upregulated in obese patients upon insulin resistance (IR) conditions, but the mechanism underlying the dysregulation of DPP4 remains unclear. This study aimed to investigate the DPP4 expression in adipose tissue and adipocytes under IR conditions or with liraglutide intervention, and explore the potential molecular mechanisms.Methods: Obesity-associated IR animal and cell models were, respectively, constructed by using high-fat diet and palmitic acid (PA) stimulation. Expression of DPP4 in adipose tissues and adipocytes was estimated by quantitative real-time RT-PCR and Western-blot. Effects of the AMPK/JAK2/STAT3 pathway on DPP4 were examined by regulating the activity of AMPK and the JAK2/STAT signaling. The therapeutic efficacy of liraglutide in the IR models was evaluated, and its regulatory effects on DPP4 expression and the underlying molecular mechanisms were explored.Results: The expression of DPP4 was markedly upregulated in both the animal and cell IR models. In the adipocyte, DPP4 expression was found to be suppressed by the activation of AMPK, and this inhibition effect was mediated by the JAK2/STAT3 signaling. Moreover, liraglutide could alleviate the obesity-induced IR, and led to the downregulation of DPP4 in IR animal and cell models. Liraglutide intervention resulted in the activation of AMPK and deactivation of the JAK2/STAT3 signaling in the adipocytes.Conclusion: Taken together, the expression of DPP4 is upregulated in adipose tissues and adipocytes upon IR conditions, but is reduced after liraglutide intervention. The dysregulation of DPP4 in the adipocytes may be performed by the AMPK/JAK2/STAT3 pathway.Keywords: obesity, adipocyte, DPP4, AMPK, JAK2/STAT3, liraglutide, insulin resistance
format	article
author	Cheng F Yuan G He J Shao Y Zhang J Guo X
author_facet	Cheng F Yuan G He J Shao Y Zhang J Guo X
author_sort	Cheng F
title	Dysregulation of DPP4 Is Associated with the AMPK/JAK2/STAT3 Pathway in Adipocytes Under Insulin Resistance Status and Liraglutide Intervention
title_short	Dysregulation of DPP4 Is Associated with the AMPK/JAK2/STAT3 Pathway in Adipocytes Under Insulin Resistance Status and Liraglutide Intervention
title_full	Dysregulation of DPP4 Is Associated with the AMPK/JAK2/STAT3 Pathway in Adipocytes Under Insulin Resistance Status and Liraglutide Intervention
title_fullStr	Dysregulation of DPP4 Is Associated with the AMPK/JAK2/STAT3 Pathway in Adipocytes Under Insulin Resistance Status and Liraglutide Intervention
title_full_unstemmed	Dysregulation of DPP4 Is Associated with the AMPK/JAK2/STAT3 Pathway in Adipocytes Under Insulin Resistance Status and Liraglutide Intervention
title_sort	dysregulation of dpp4 is associated with the ampk/jak2/stat3 pathway in adipocytes under insulin resistance status and liraglutide intervention
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/eab2571805934175a738ba9512894384
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Dysregulation of DPP4 Is Associated with the AMPK/JAK2/STAT3 Pathway in Adipocytes Under Insulin Resistance Status and Liraglutide Intervention

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