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LPS-Induced Inhibition of miR-143 Expression in Brown Adipocytes Promotes Thermogenesis and Fever

Fever is an important part of inflammatory response to infection. Although brown adipose tissue (BAT) thermogenesis is known to be potently influenced by systemic inflammation, the role of BAT during infection-induced fever remains largely unknown. Here, we injected mice with a low dose of LPS and f...

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Autores principales: Liu, Jie, Zeng, Dewei, Luo, Junyi, Wang, Huan, Xiong, Jiali, Chen, Xingping, Chen, Ting, Sun, Jiajie, Xi, Qianyun, Zhang, Yongliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696956/
https://www.ncbi.nlm.nih.gov/pubmed/36430282
http://dx.doi.org/10.3390/ijms232213805
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author Liu, Jie
Zeng, Dewei
Luo, Junyi
Wang, Huan
Xiong, Jiali
Chen, Xingping
Chen, Ting
Sun, Jiajie
Xi, Qianyun
Zhang, Yongliang
author_facet Liu, Jie
Zeng, Dewei
Luo, Junyi
Wang, Huan
Xiong, Jiali
Chen, Xingping
Chen, Ting
Sun, Jiajie
Xi, Qianyun
Zhang, Yongliang
author_sort Liu, Jie
collection PubMed
description Fever is an important part of inflammatory response to infection. Although brown adipose tissue (BAT) thermogenesis is known to be potently influenced by systemic inflammation, the role of BAT during infection-induced fever remains largely unknown. Here, we injected mice with a low dose of LPS and found that low-dose LPS can directly induce thermogenesis of brown adipocytes. It is known that miR-143 is highly expressed in the BAT, and miR-143 knockout mice exhibited stronger thermogenesis under cold exposure. Interestingly, miR-143 was negatively correlated with an LPS-induced increase of TNFα and IL-6 mRNA levels, and the IL-6 pathway may mediate the inhibition of miR-143 expression. Moreover, miR-143 is down-regulated by LPS, and overexpression of miR-143 in brown adipocytes by lentivirus could rescue the enhancement of UCP1 protein expression caused by LPS, hinting miR-143 may be an important regulator of the thermogenesis in brown adipocytes. More importantly, the knockout of miR-143 further enhanced the LPS-induced increase of body temperature and BAT thermogenesis, and this result was further confirmed by in vitro experiments by using primary brown adipocytes. Mechanistically, adenylate cyclase 9 (AC9) is a new target gene of miR-143 and LPS increases BAT thermogenesis by a way of inhibiting miR-143 expression, a negative regulator for AC9. Our study considerably improves our collective understanding of the important function of miR-143 in inflammatory BAT thermogenesis.
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spelling pubmed-96969562022-11-26 LPS-Induced Inhibition of miR-143 Expression in Brown Adipocytes Promotes Thermogenesis and Fever Liu, Jie Zeng, Dewei Luo, Junyi Wang, Huan Xiong, Jiali Chen, Xingping Chen, Ting Sun, Jiajie Xi, Qianyun Zhang, Yongliang Int J Mol Sci Article Fever is an important part of inflammatory response to infection. Although brown adipose tissue (BAT) thermogenesis is known to be potently influenced by systemic inflammation, the role of BAT during infection-induced fever remains largely unknown. Here, we injected mice with a low dose of LPS and found that low-dose LPS can directly induce thermogenesis of brown adipocytes. It is known that miR-143 is highly expressed in the BAT, and miR-143 knockout mice exhibited stronger thermogenesis under cold exposure. Interestingly, miR-143 was negatively correlated with an LPS-induced increase of TNFα and IL-6 mRNA levels, and the IL-6 pathway may mediate the inhibition of miR-143 expression. Moreover, miR-143 is down-regulated by LPS, and overexpression of miR-143 in brown adipocytes by lentivirus could rescue the enhancement of UCP1 protein expression caused by LPS, hinting miR-143 may be an important regulator of the thermogenesis in brown adipocytes. More importantly, the knockout of miR-143 further enhanced the LPS-induced increase of body temperature and BAT thermogenesis, and this result was further confirmed by in vitro experiments by using primary brown adipocytes. Mechanistically, adenylate cyclase 9 (AC9) is a new target gene of miR-143 and LPS increases BAT thermogenesis by a way of inhibiting miR-143 expression, a negative regulator for AC9. Our study considerably improves our collective understanding of the important function of miR-143 in inflammatory BAT thermogenesis. MDPI 2022-11-09 /pmc/articles/PMC9696956/ /pubmed/36430282 http://dx.doi.org/10.3390/ijms232213805 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Jie
Zeng, Dewei
Luo, Junyi
Wang, Huan
Xiong, Jiali
Chen, Xingping
Chen, Ting
Sun, Jiajie
Xi, Qianyun
Zhang, Yongliang
LPS-Induced Inhibition of miR-143 Expression in Brown Adipocytes Promotes Thermogenesis and Fever
title LPS-Induced Inhibition of miR-143 Expression in Brown Adipocytes Promotes Thermogenesis and Fever
title_full LPS-Induced Inhibition of miR-143 Expression in Brown Adipocytes Promotes Thermogenesis and Fever
title_fullStr LPS-Induced Inhibition of miR-143 Expression in Brown Adipocytes Promotes Thermogenesis and Fever
title_full_unstemmed LPS-Induced Inhibition of miR-143 Expression in Brown Adipocytes Promotes Thermogenesis and Fever
title_short LPS-Induced Inhibition of miR-143 Expression in Brown Adipocytes Promotes Thermogenesis and Fever
title_sort lps-induced inhibition of mir-143 expression in brown adipocytes promotes thermogenesis and fever
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696956/
https://www.ncbi.nlm.nih.gov/pubmed/36430282
http://dx.doi.org/10.3390/ijms232213805
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