Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance

Xuxiang Zhang,1 Yuming Wang,2 Fan Zuo,1 Yandan Su,3 Hua Liu,3 Bin Wu,1 Xin Nian1 1Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Clinical Laboratory, Second Affiliated Hospital of Kunming Med...

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Autores principales:	Zhang X, Wang Y, Zuo F, Su Y, Liu H, Wu B, Nian X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	foxc2 expression regulation adipocyte differentiation insulin resistance Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/8d81532be5fb4d8396f3c02e14c39746
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spelling	oai:doaj.org-article:8d81532be5fb4d8396f3c02e14c397462021-12-02T08:41:21ZEffect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance1178-7007https://doaj.org/article/8d81532be5fb4d8396f3c02e14c397462020-08-01T00:00:00Zhttps://www.dovepress.com/effect-of-insulin-regulated-foxc2-expression-in-adipocyte-differentiat-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Xuxiang Zhang,1 Yuming Wang,2 Fan Zuo,1 Yandan Su,3 Hua Liu,3 Bin Wu,1 Xin Nian1 1Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Clinical Laboratory, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Xin NianDepartment of Endocrinology, First Affiliated Hospital of Kunming Medical University Email nianxinkm@hotmail.comObjective: 1) To investigate the effect of FOXC2 on the differentiation of adipose-derived mesenchymal stem cells. 2) To analyze the mechanism between FOXC2 expression regulation in adipose differentiation and insulin resistance (IR).Methods: We first amplified the FOXC2 promoter region-512 and cloned it into the luciferase expression vector. The reporter gene system was transfected into the adipose tissue-derived mesenchymal stem cell to study insulin-mediated FOXC2 expression. We also manipulated FOXC2 protein expression by either siRNA or overexpression and studied the differentiation capability of adipose tissue-derived mesenchymal stem cell into adipocytes, as well as the influence on several IR-related genes: GLUT4, PPARγ, UCP1 and PAI-1.Results: 1) Insulin effectively induced the expression of FOXC2 protein in adipose tissue-derived mesenchymal stem cells under differentiation (P< 0.01). Insulin also induced FOXC2-pro-512T promoter activity significantly (P< 0.01). 2) The stem cell adipose differentiation decreased in the FOXC2 overexpression group. 3) When FOXC2 was overexpressed, the expression of GLUT4, PAI-1 and UCP1 was higher than control groups (p< 0.001). When FOXC2 was down-regulated by siRNA, both GLUT4 and PAI-1’s protein expression were decreased (p< 0.001), and the protein expression of PPARγ was increased (p< 0.001). In the presence of insulin induction, overexpression of FOXC2 led to significantly higher UCP-1 expression (p< 0.001) and lower PAI-1 expression (p< 0.001). The protein expression of GLUT4, PAI-1 (p< 0.001) and UCP-1 (p< 0.05) was decreased in cells transfected with FOXC2 siRNA.Conclusion: Insulin effectively induced the expression of FOXC2 protein in adipose tissue-derived mesenchymal stem cells under differentiation, possibly through the regulation of the FOXC2-pro-512T promoter activity. The different protein expression of FOXC2 has regulatory effects on several genes related to insulin resistance. FOXC2 is an important regulatory factor in adipocyte differentiation and insulin resistance.Keywords: FOXC2, expression regulation, adipocyte differentiation, insulin resistanceZhang XWang YZuo FSu YLiu HWu BNian XDove Medical Pressarticlefoxc2expression regulationadipocyte differentiationinsulin resistanceSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 2801-2809 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	foxc2 expression regulation adipocyte differentiation insulin resistance Specialties of internal medicine RC581-951
spellingShingle	foxc2 expression regulation adipocyte differentiation insulin resistance Specialties of internal medicine RC581-951 Zhang X Wang Y Zuo F Su Y Liu H Wu B Nian X Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance
description	Xuxiang Zhang,1 Yuming Wang,2 Fan Zuo,1 Yandan Su,3 Hua Liu,3 Bin Wu,1 Xin Nian1 1Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Clinical Laboratory, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Xin NianDepartment of Endocrinology, First Affiliated Hospital of Kunming Medical University Email nianxinkm@hotmail.comObjective: 1) To investigate the effect of FOXC2 on the differentiation of adipose-derived mesenchymal stem cells. 2) To analyze the mechanism between FOXC2 expression regulation in adipose differentiation and insulin resistance (IR).Methods: We first amplified the FOXC2 promoter region-512 and cloned it into the luciferase expression vector. The reporter gene system was transfected into the adipose tissue-derived mesenchymal stem cell to study insulin-mediated FOXC2 expression. We also manipulated FOXC2 protein expression by either siRNA or overexpression and studied the differentiation capability of adipose tissue-derived mesenchymal stem cell into adipocytes, as well as the influence on several IR-related genes: GLUT4, PPARγ, UCP1 and PAI-1.Results: 1) Insulin effectively induced the expression of FOXC2 protein in adipose tissue-derived mesenchymal stem cells under differentiation (P< 0.01). Insulin also induced FOXC2-pro-512T promoter activity significantly (P< 0.01). 2) The stem cell adipose differentiation decreased in the FOXC2 overexpression group. 3) When FOXC2 was overexpressed, the expression of GLUT4, PAI-1 and UCP1 was higher than control groups (p< 0.001). When FOXC2 was down-regulated by siRNA, both GLUT4 and PAI-1’s protein expression were decreased (p< 0.001), and the protein expression of PPARγ was increased (p< 0.001). In the presence of insulin induction, overexpression of FOXC2 led to significantly higher UCP-1 expression (p< 0.001) and lower PAI-1 expression (p< 0.001). The protein expression of GLUT4, PAI-1 (p< 0.001) and UCP-1 (p< 0.05) was decreased in cells transfected with FOXC2 siRNA.Conclusion: Insulin effectively induced the expression of FOXC2 protein in adipose tissue-derived mesenchymal stem cells under differentiation, possibly through the regulation of the FOXC2-pro-512T promoter activity. The different protein expression of FOXC2 has regulatory effects on several genes related to insulin resistance. FOXC2 is an important regulatory factor in adipocyte differentiation and insulin resistance.Keywords: FOXC2, expression regulation, adipocyte differentiation, insulin resistance
format	article
author	Zhang X Wang Y Zuo F Su Y Liu H Wu B Nian X
author_facet	Zhang X Wang Y Zuo F Su Y Liu H Wu B Nian X
author_sort	Zhang X
title	Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance
title_short	Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance
title_full	Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance
title_fullStr	Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance
title_full_unstemmed	Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance
title_sort	effect of insulin-regulated foxc2 expression in adipocyte differentiation and insulin resistance
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/8d81532be5fb4d8396f3c02e14c39746
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Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance

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