TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice

Abstract Recent studies have shown that overexpression of tonicity-responsive enhancer binding protein (TonEBP) is associated with many inflammatory diseases, including diabetes mellitus, which causes neuroinflammation in the hippocampus as well as hepatic steatosis. However, the exact mechanism in...

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Autores principales:	Jong Youl Lee, Eun Ae Jeong, Kyung Eun Kim, Chin-ok Yi, Zhen Jin, Jung Eun Lee, Dong Hoon Lee, Hyun Joon Kim, Sang Soo Kang, Gyeong Jae Cho, Wan Sung Choi, Soo Youn Choi, H. Moo Kwon, Gu Seob Roh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ec10050aa8ec4c0993ff33816e9eaeeb
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spelling	oai:doaj.org-article:ec10050aa8ec4c0993ff33816e9eaeeb2021-12-02T11:41:10ZTonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice10.1038/s41598-017-08319-w2045-2322https://doaj.org/article/ec10050aa8ec4c0993ff33816e9eaeeb2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08319-whttps://doaj.org/toc/2045-2322Abstract Recent studies have shown that overexpression of tonicity-responsive enhancer binding protein (TonEBP) is associated with many inflammatory diseases, including diabetes mellitus, which causes neuroinflammation in the hippocampus as well as hepatic steatosis. However, the exact mechanism in diabetic neuroinflammation is unknown. We report that haploinsufficiency of TonEBP inhibits hepatic and hippocampal high-mobility group box-1 (HMGB1) expression in diabetic mice. Here, mice were fed a high-fat diet (HFD) for 16 weeks and received an intraperitoneal injection of 100 mg/kg streptozotocin (STZ) and followed by continued HFD feeding for an additional 4 weeks to induce hyperglycemia and hepatic steatosis. Compared with wild-type diabetic mice, diabetic TonEBP+/− mice showed decreased body weight, fat mass, hepatic steatosis, and macrophage infiltration. We also found that adipogenesis and HMGB1 expression in the liver and hippocampus were lower in diabetic TonEBP+/− mice compared with the wild type. Furthermore, iba-1 immunoreactivity in the hippocampus was decreased in diabetic TonEBP+/− mice compared with that in the wild type. Our findings suggest that TonEBP haploinsufficiency suppresses diabetes-associated hepatic steatosis and neuroinflammation.Jong Youl LeeEun Ae JeongKyung Eun KimChin-ok YiZhen JinJung Eun LeeDong Hoon LeeHyun Joon KimSang Soo KangGyeong Jae ChoWan Sung ChoiSoo Youn ChoiH. Moo KwonGu Seob RohNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jong Youl Lee Eun Ae Jeong Kyung Eun Kim Chin-ok Yi Zhen Jin Jung Eun Lee Dong Hoon Lee Hyun Joon Kim Sang Soo Kang Gyeong Jae Cho Wan Sung Choi Soo Youn Choi H. Moo Kwon Gu Seob Roh TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice
description	Abstract Recent studies have shown that overexpression of tonicity-responsive enhancer binding protein (TonEBP) is associated with many inflammatory diseases, including diabetes mellitus, which causes neuroinflammation in the hippocampus as well as hepatic steatosis. However, the exact mechanism in diabetic neuroinflammation is unknown. We report that haploinsufficiency of TonEBP inhibits hepatic and hippocampal high-mobility group box-1 (HMGB1) expression in diabetic mice. Here, mice were fed a high-fat diet (HFD) for 16 weeks and received an intraperitoneal injection of 100 mg/kg streptozotocin (STZ) and followed by continued HFD feeding for an additional 4 weeks to induce hyperglycemia and hepatic steatosis. Compared with wild-type diabetic mice, diabetic TonEBP+/− mice showed decreased body weight, fat mass, hepatic steatosis, and macrophage infiltration. We also found that adipogenesis and HMGB1 expression in the liver and hippocampus were lower in diabetic TonEBP+/− mice compared with the wild type. Furthermore, iba-1 immunoreactivity in the hippocampus was decreased in diabetic TonEBP+/− mice compared with that in the wild type. Our findings suggest that TonEBP haploinsufficiency suppresses diabetes-associated hepatic steatosis and neuroinflammation.
format	article
author	Jong Youl Lee Eun Ae Jeong Kyung Eun Kim Chin-ok Yi Zhen Jin Jung Eun Lee Dong Hoon Lee Hyun Joon Kim Sang Soo Kang Gyeong Jae Cho Wan Sung Choi Soo Youn Choi H. Moo Kwon Gu Seob Roh
author_facet	Jong Youl Lee Eun Ae Jeong Kyung Eun Kim Chin-ok Yi Zhen Jin Jung Eun Lee Dong Hoon Lee Hyun Joon Kim Sang Soo Kang Gyeong Jae Cho Wan Sung Choi Soo Youn Choi H. Moo Kwon Gu Seob Roh
author_sort	Jong Youl Lee
title	TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice
title_short	TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice
title_full	TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice
title_fullStr	TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice
title_full_unstemmed	TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice
title_sort	tonebp/nfat5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ec10050aa8ec4c0993ff33816e9eaeeb
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TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice

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