دورية أكاديمية
Pemafibrate suppresses NLRP3 inflammasome activation in the liver and heart in a novel mouse model of steatohepatitis-related cardiomyopathy
| العنوان: | Pemafibrate suppresses NLRP3 inflammasome activation in the liver and heart in a novel mouse model of steatohepatitis-related cardiomyopathy |
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| المؤلفون: | Kotaro Kanno, Masahiro Koseki, Jiuyang Chang, Ayami Saga, Hiroyasu Inui, Takeshi Okada, Katsunao Tanaka, Masumi Asaji, Yinghong Zhu, Seiko Ide, Shigeyoshi Saito, Tomoaki Higo, Daisuke Okuzaki, Tohru Ohama, Makoto Nishida, Yoshihiro Kamada, Masafumi Ono, Toshiji Saibara, Shizuya Yamashita, Yasushi Sakata |
| المصدر: | Scientific Reports, Vol 12, Iss 1, Pp 1-17 (2022) |
| بيانات النشر: | Nature Portfolio, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Although patients with nonalcoholic fatty liver disease have been reported to have cardiac dysfunction, and appropriate model has not been reported. We established a novel mouse model of diet-induced steatohepatitis-related cardiomyopathy and evaluated the effect of pemafibrate. C57Bl/6 male mice were fed a (1) chow diet (C), (2) high-fat, high-cholesterol, high-sucrose, bile acid diet (NASH diet; N), or (3) N with pemafibrate 0.1 mg/kg (NP) for 8 weeks. In the liver, macrophage infiltration and fibrosis in the liver was observed in the N group compared to the C group, suggesting steatohepatitis. Free cholesterol accumulated, and cholesterol crystals were observed. In the heart, free cholesterol similarly accumulated and concentric hypertrophy was observed. Ultrahigh magnetic field magnetic resonance imaging revealed that the left ventricular (LV) ejection fraction (EF) was attenuated and LV strain was focally impaired. RNA sequencing demonstrated that the NOD-like receptor and PI3 kinase-Akt pathways were enhanced. mRNA and protein expression of inflammasome-related genes, such as Caspase-1, NLRP3, and IL-1β, were upregulated in both the liver and heart. In the NP compared to the N group, steatohepatitis, hepatic steatosis, and cardiac dysfunction were suppressed. Sequential administration of pemafibrate after the development of steatohepatitis-related cardiomyopathy recovered hepatic fibrosis and cardiac dysfunction. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-022-06542-8 |
| URL الوصول: | https://doaj.org/article/f417ef3745a84a19b9a8a2bc5596ce26 |
| رقم الأكسشن: | edsdoj.f417ef3745a84a19b9a8a2bc5596ce26 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-022-06542-8 |