PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes

Abstract Background Obesity-induced elevated serum free fatty acids (FFAs) levels result in the occurrence of type 2 diabetes mellitus (T2DM). However, the molecular mechanism remains largely enigmatic. This study was to explore the effect and mechanism of KLF15 on FFAs-induced abnormal glucose meta...

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Autores principales:	Cuizhe Wang, Xiaolong Chu, Yuchun Deng, Jingzhou Wang, Tongtong Qiu, Jiaojiao Zhu, Xin Yang, Chongge Pan, Jianyu Xiong, Jianxin Xie, Yongsheng Chang, Jun Zhang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Obesity Palmitic acid Oleic acid Adipocyte KLF15 Nutrition. Foods and food supply TX341-641 Nutritional diseases. Deficiency diseases RC620-627
Acceso en línea:	https://doaj.org/article/10c6f0560c7643fba4fc7c3d18873695
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spelling	oai:doaj.org-article:10c6f0560c7643fba4fc7c3d188736952021-11-28T12:13:37ZPA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes10.1186/s12986-021-00628-21743-7075https://doaj.org/article/10c6f0560c7643fba4fc7c3d188736952021-11-01T00:00:00Zhttps://doi.org/10.1186/s12986-021-00628-2https://doaj.org/toc/1743-7075Abstract Background Obesity-induced elevated serum free fatty acids (FFAs) levels result in the occurrence of type 2 diabetes mellitus (T2DM). However, the molecular mechanism remains largely enigmatic. This study was to explore the effect and mechanism of KLF15 on FFAs-induced abnormal glucose metabolism. Methods Levels of TG, TC, HDL-C, LDL-C, and glucose were measured by different assay kits. qRT-PCR and Western Blot were used to detect the levels of GPR120, GPR40, phosphorylation of p38 MAPK, KLF15, and downstream factors. Results KLF15 was decreased in visceral adipose tissue of obesity subjects and high-fat diet (HFD) mice. In HFD mice, GPR120 antagonist significantly promoted KLF15 protein expression level and phosphorylation of p38 MAPK, meanwhile reduced the blood glucose levels. While, blocking GPR40 inhibited the KLF15 expression. In 3T3-L1 adipocytes, 1500 μM PA inhibited KLF15 through a GPR120/P-p38 MAPK signal pathway, and 750 μM OA inhibited KLF15 mainly through GPR120 while not dependent on P-p38 MAPK, ultimately resulting in abnormal glucose metabolism. Unfortunately, GPR40 didn’t contribute to PA or OA-induced KLF15 reduction. Conclusions Both PA and OA inhibit KLF15 expression through GPR120, leading to abnormal glucose metabolism in adipocytes. Notably, the inhibition of KLF15 expression by PA depends on phosphorylation of p38 MAPK.Cuizhe WangXiaolong ChuYuchun DengJingzhou WangTongtong QiuJiaojiao ZhuXin YangChongge PanJianyu XiongJianxin XieYongsheng ChangJun ZhangBMCarticleObesityPalmitic acidOleic acidAdipocyteKLF15Nutrition. Foods and food supplyTX341-641Nutritional diseases. Deficiency diseasesRC620-627ENNutrition & Metabolism, Vol 18, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Obesity Palmitic acid Oleic acid Adipocyte KLF15 Nutrition. Foods and food supply TX341-641 Nutritional diseases. Deficiency diseases RC620-627
spellingShingle	Obesity Palmitic acid Oleic acid Adipocyte KLF15 Nutrition. Foods and food supply TX341-641 Nutritional diseases. Deficiency diseases RC620-627 Cuizhe Wang Xiaolong Chu Yuchun Deng Jingzhou Wang Tongtong Qiu Jiaojiao Zhu Xin Yang Chongge Pan Jianyu Xiong Jianxin Xie Yongsheng Chang Jun Zhang PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes
description	Abstract Background Obesity-induced elevated serum free fatty acids (FFAs) levels result in the occurrence of type 2 diabetes mellitus (T2DM). However, the molecular mechanism remains largely enigmatic. This study was to explore the effect and mechanism of KLF15 on FFAs-induced abnormal glucose metabolism. Methods Levels of TG, TC, HDL-C, LDL-C, and glucose were measured by different assay kits. qRT-PCR and Western Blot were used to detect the levels of GPR120, GPR40, phosphorylation of p38 MAPK, KLF15, and downstream factors. Results KLF15 was decreased in visceral adipose tissue of obesity subjects and high-fat diet (HFD) mice. In HFD mice, GPR120 antagonist significantly promoted KLF15 protein expression level and phosphorylation of p38 MAPK, meanwhile reduced the blood glucose levels. While, blocking GPR40 inhibited the KLF15 expression. In 3T3-L1 adipocytes, 1500 μM PA inhibited KLF15 through a GPR120/P-p38 MAPK signal pathway, and 750 μM OA inhibited KLF15 mainly through GPR120 while not dependent on P-p38 MAPK, ultimately resulting in abnormal glucose metabolism. Unfortunately, GPR40 didn’t contribute to PA or OA-induced KLF15 reduction. Conclusions Both PA and OA inhibit KLF15 expression through GPR120, leading to abnormal glucose metabolism in adipocytes. Notably, the inhibition of KLF15 expression by PA depends on phosphorylation of p38 MAPK.
format	article
author	Cuizhe Wang Xiaolong Chu Yuchun Deng Jingzhou Wang Tongtong Qiu Jiaojiao Zhu Xin Yang Chongge Pan Jianyu Xiong Jianxin Xie Yongsheng Chang Jun Zhang
author_facet	Cuizhe Wang Xiaolong Chu Yuchun Deng Jingzhou Wang Tongtong Qiu Jiaojiao Zhu Xin Yang Chongge Pan Jianyu Xiong Jianxin Xie Yongsheng Chang Jun Zhang
author_sort	Cuizhe Wang
title	PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes
title_short	PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes
title_full	PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes
title_fullStr	PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes
title_full_unstemmed	PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes
title_sort	pa and oa induce abnormal glucose metabolism by inhibiting klf15 in adipocytes
publisher	BMC
publishDate	2021
url	https://doaj.org/article/10c6f0560c7643fba4fc7c3d18873695
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_version_	1718408121775292416

PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes

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