TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation

Abstract Obesity and high-fat diet (HFD) consumption result in hypothalamic inflammation and metabolic dysfunction. While the TLR4 activation by dietary fats is a well-characterized pathway involved in the neuronal and glial inflammation, the role of its accessory proteins in diet-induced hypothalam...

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Autores principales:	Alexandre Moura-Assis, Pedro A. S. Nogueira, Jose C. de-Lima-Junior, Fernando M. Simabuco, Joana M. Gaspar, Jose Donato Jr, Licio A. Velloso
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4adeb126c7c44bf4944aa30208fa4da4
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spelling	oai:doaj.org-article:4adeb126c7c44bf4944aa30208fa4da42021-12-02T17:41:13ZTLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation10.1038/s41598-021-97291-72045-2322https://doaj.org/article/4adeb126c7c44bf4944aa30208fa4da42021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97291-7https://doaj.org/toc/2045-2322Abstract Obesity and high-fat diet (HFD) consumption result in hypothalamic inflammation and metabolic dysfunction. While the TLR4 activation by dietary fats is a well-characterized pathway involved in the neuronal and glial inflammation, the role of its accessory proteins in diet-induced hypothalamic inflammation remains unknown. Here, we demonstrate that the knockdown of TLR4-interactor with leucine-rich repeats (Tril), a functional component of TLR4, resulted in reduced hypothalamic inflammation, increased whole-body energy expenditure, improved the systemic glucose tolerance and protection from diet-induced obesity. The POMC-specific knockdown of Tril resulted in decreased body fat, decreased white adipose tissue inflammation and a trend toward increased leptin signaling in POMC neurons. Thus, Tril was identified as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental obesity and its inhibition in the hypothalamus may represent a novel target for obesity treatment.Alexandre Moura-AssisPedro A. S. NogueiraJose C. de-Lima-JuniorFernando M. SimabucoJoana M. GasparJose Donato JrLicio A. VellosoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexandre Moura-Assis Pedro A. S. Nogueira Jose C. de-Lima-Junior Fernando M. Simabuco Joana M. Gaspar Jose Donato Jr Licio A. Velloso TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation
description	Abstract Obesity and high-fat diet (HFD) consumption result in hypothalamic inflammation and metabolic dysfunction. While the TLR4 activation by dietary fats is a well-characterized pathway involved in the neuronal and glial inflammation, the role of its accessory proteins in diet-induced hypothalamic inflammation remains unknown. Here, we demonstrate that the knockdown of TLR4-interactor with leucine-rich repeats (Tril), a functional component of TLR4, resulted in reduced hypothalamic inflammation, increased whole-body energy expenditure, improved the systemic glucose tolerance and protection from diet-induced obesity. The POMC-specific knockdown of Tril resulted in decreased body fat, decreased white adipose tissue inflammation and a trend toward increased leptin signaling in POMC neurons. Thus, Tril was identified as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental obesity and its inhibition in the hypothalamus may represent a novel target for obesity treatment.
format	article
author	Alexandre Moura-Assis Pedro A. S. Nogueira Jose C. de-Lima-Junior Fernando M. Simabuco Joana M. Gaspar Jose Donato Jr Licio A. Velloso
author_facet	Alexandre Moura-Assis Pedro A. S. Nogueira Jose C. de-Lima-Junior Fernando M. Simabuco Joana M. Gaspar Jose Donato Jr Licio A. Velloso
author_sort	Alexandre Moura-Assis
title	TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation
title_short	TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation
title_full	TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation
title_fullStr	TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation
title_full_unstemmed	TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation
title_sort	tlr4-interactor with leucine-rich repeats (tril) is involved in diet-induced hypothalamic inflammation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4adeb126c7c44bf4944aa30208fa4da4
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TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation

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