5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes

Abstract Leukotriene B4 (LTB4) production via the 5-lipoxygenase (5-LO) pathway contributes to the development of insulin resistance in adipose and hepatic tissues, but the role of LTB4 in skeletal muscle is relatively unknown. Here, the authors investigated the role of LTB4 in C2C12 myotubes in pal...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hyun Jeong Kwak, Hye-Eun Choi, Hyae Gyeong Cheon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2048fc0877bd4c1cb61650a06aa52d34
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2048fc0877bd4c1cb61650a06aa52d34
record_format	dspace
spelling	oai:doaj.org-article:2048fc0877bd4c1cb61650a06aa52d342021-12-02T11:52:33Z5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes10.1038/s41598-017-05346-52045-2322https://doaj.org/article/2048fc0877bd4c1cb61650a06aa52d342017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05346-5https://doaj.org/toc/2045-2322Abstract Leukotriene B4 (LTB4) production via the 5-lipoxygenase (5-LO) pathway contributes to the development of insulin resistance in adipose and hepatic tissues, but the role of LTB4 in skeletal muscle is relatively unknown. Here, the authors investigated the role of LTB4 in C2C12 myotubes in palmitic acid (PA)-induced ER stress, inflammation and insulin resistance. PA (750 μM) evoked lipotoxicity (ER stress, oxidative stress, inflammation and insulin resistance) in association with LTB4 production. 5-LO inhibition reduced all the lipotoxic effects induced by PA. On the other hand, PA did not induce cysteinyl leukotrienes (CysLTs), which themselves had no effect on ER stress and inflammation. The beneficial effects of 5-LO suppression from PA-induced lipotoxicity were related with AMPK activation. In ob/ob mice, once daily oral administration of zileuton (50, 100 mg/kg) for 5 weeks improved insulin resistance, increased AMPK phosphorylation, and reduced LTB4 and ER stress marker expression in skeletal muscle. These results show that 5-LO inhibition by either zileuton or 5-LO siRNA protects C2C12 myotubes from PA-induced lipotoxicity, at least partly via AMPK activation, and suggest that the in vivo insulin-sensitizing effects of zileuton are in part attributable to its direct action on skeletal muscle via LTB4 downregulation followed by AMPK activation.Hyun Jeong KwakHye-Eun ChoiHyae Gyeong CheonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hyun Jeong Kwak Hye-Eun Choi Hyae Gyeong Cheon 5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes
description	Abstract Leukotriene B4 (LTB4) production via the 5-lipoxygenase (5-LO) pathway contributes to the development of insulin resistance in adipose and hepatic tissues, but the role of LTB4 in skeletal muscle is relatively unknown. Here, the authors investigated the role of LTB4 in C2C12 myotubes in palmitic acid (PA)-induced ER stress, inflammation and insulin resistance. PA (750 μM) evoked lipotoxicity (ER stress, oxidative stress, inflammation and insulin resistance) in association with LTB4 production. 5-LO inhibition reduced all the lipotoxic effects induced by PA. On the other hand, PA did not induce cysteinyl leukotrienes (CysLTs), which themselves had no effect on ER stress and inflammation. The beneficial effects of 5-LO suppression from PA-induced lipotoxicity were related with AMPK activation. In ob/ob mice, once daily oral administration of zileuton (50, 100 mg/kg) for 5 weeks improved insulin resistance, increased AMPK phosphorylation, and reduced LTB4 and ER stress marker expression in skeletal muscle. These results show that 5-LO inhibition by either zileuton or 5-LO siRNA protects C2C12 myotubes from PA-induced lipotoxicity, at least partly via AMPK activation, and suggest that the in vivo insulin-sensitizing effects of zileuton are in part attributable to its direct action on skeletal muscle via LTB4 downregulation followed by AMPK activation.
format	article
author	Hyun Jeong Kwak Hye-Eun Choi Hyae Gyeong Cheon
author_facet	Hyun Jeong Kwak Hye-Eun Choi Hyae Gyeong Cheon
author_sort	Hyun Jeong Kwak
title	5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes
title_short	5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes
title_full	5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes
title_fullStr	5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes
title_full_unstemmed	5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes
title_sort	5-lo inhibition ameliorates palmitic acid-induced er stress, oxidative stress and insulin resistance via ampk activation in murine myotubes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2048fc0877bd4c1cb61650a06aa52d34
work_keys_str_mv	AT hyunjeongkwak 5loinhibitionamelioratespalmiticacidinducederstressoxidativestressandinsulinresistanceviaampkactivationinmurinemyotubes AT hyeeunchoi 5loinhibitionamelioratespalmiticacidinducederstressoxidativestressandinsulinresistanceviaampkactivationinmurinemyotubes AT hyaegyeongcheon 5loinhibitionamelioratespalmiticacidinducederstressoxidativestressandinsulinresistanceviaampkactivationinmurinemyotubes
_version_	1718394970975502336

5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes

Ejemplares similares