Knockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders

Abstract High-fat diet-induced hypothalamic metabolic inflammation is emerging as a cause for the development of obesity. It is acknowledged that Toll-like receptor4 (TLR4) signaling plays a crucial role in triggering of the hypothalamic metabolic inflammation during the course of diet-induced obesi...

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Autores principales:	Yongli Zhao, Guohua Li, Ying Li, Yuchuan Wang, Zhengjuan Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/55a383b6afce4a87959fa17f5371a1f8
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spelling	oai:doaj.org-article:55a383b6afce4a87959fa17f5371a1f82021-12-02T12:32:20ZKnockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders10.1038/s41598-017-07858-62045-2322https://doaj.org/article/55a383b6afce4a87959fa17f5371a1f82017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07858-6https://doaj.org/toc/2045-2322Abstract High-fat diet-induced hypothalamic metabolic inflammation is emerging as a cause for the development of obesity. It is acknowledged that Toll-like receptor4 (TLR4) signaling plays a crucial role in triggering of the hypothalamic metabolic inflammation during the course of diet-induced obesity. Whether hypothalamic arcuate nucleus (ARC)-restricted TLR4 knockdown improves obesity-related metabolic disorders remains unexplored. In this study, we used TLR4 shRNA lentiviral particles to suppress the TLR4 expression in the hypothalamic ARC of diet-induced obese rat model by stereotaxic injection. Our results demonstrate that ARC-restricted TLR4 knockdown protects obese rats from diet-induced weight gain and energy intake, from diet-induced impaired glucose homeostasis and peripheral insulin resistance, and from high-fat diet-induced hepatic steatosis and adipocyte hypertrophy. Thus, we define ARC-restricted TLR4 knockdown as a potential strategy to combat metabolic disorders associated with obesity.Yongli ZhaoGuohua LiYing LiYuchuan WangZhengjuan LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yongli Zhao Guohua Li Ying Li Yuchuan Wang Zhengjuan Liu Knockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders
description	Abstract High-fat diet-induced hypothalamic metabolic inflammation is emerging as a cause for the development of obesity. It is acknowledged that Toll-like receptor4 (TLR4) signaling plays a crucial role in triggering of the hypothalamic metabolic inflammation during the course of diet-induced obesity. Whether hypothalamic arcuate nucleus (ARC)-restricted TLR4 knockdown improves obesity-related metabolic disorders remains unexplored. In this study, we used TLR4 shRNA lentiviral particles to suppress the TLR4 expression in the hypothalamic ARC of diet-induced obese rat model by stereotaxic injection. Our results demonstrate that ARC-restricted TLR4 knockdown protects obese rats from diet-induced weight gain and energy intake, from diet-induced impaired glucose homeostasis and peripheral insulin resistance, and from high-fat diet-induced hepatic steatosis and adipocyte hypertrophy. Thus, we define ARC-restricted TLR4 knockdown as a potential strategy to combat metabolic disorders associated with obesity.
format	article
author	Yongli Zhao Guohua Li Ying Li Yuchuan Wang Zhengjuan Liu
author_facet	Yongli Zhao Guohua Li Ying Li Yuchuan Wang Zhengjuan Liu
author_sort	Yongli Zhao
title	Knockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders
title_short	Knockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders
title_full	Knockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders
title_fullStr	Knockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders
title_full_unstemmed	Knockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders
title_sort	knockdown of tlr4 in the arcuate nucleus improves obesity related metabolic disorders
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/55a383b6afce4a87959fa17f5371a1f8
work_keys_str_mv	AT yonglizhao knockdownoftlr4inthearcuatenucleusimprovesobesityrelatedmetabolicdisorders AT guohuali knockdownoftlr4inthearcuatenucleusimprovesobesityrelatedmetabolicdisorders AT yingli knockdownoftlr4inthearcuatenucleusimprovesobesityrelatedmetabolicdisorders AT yuchuanwang knockdownoftlr4inthearcuatenucleusimprovesobesityrelatedmetabolicdisorders AT zhengjuanliu knockdownoftlr4inthearcuatenucleusimprovesobesityrelatedmetabolicdisorders
_version_	1718394094131085312

Knockdown of Tlr4 in the Arcuate Nucleus Improves Obesity Related Metabolic Disorders

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