Notch1 haploinsufficiency in mice accelerates adipogenesis

Abstract Notch signaling has been recognized recently as a key regulator of metabolism. Here, we determined the role of Notch1 in adipogenesis in wild-type (WT) and Notch1 hetero-mutant (N1+/−) mice provided with 12-week normal or high-fat diet. Haploinsufficiency of Notch1 was associated with adipo...

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Autores principales:	Kazutoshi Yamaguchi, Motoharu Hayashi, Yasuhiro Uchida, Xian Wu Cheng, Takayuki Nakayama, Tadashi Matsushita, Toyoaki Murohara, Kyosuke Takeshita
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1f7ab7957a43406f90deeb9940a1187c
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spelling	oai:doaj.org-article:1f7ab7957a43406f90deeb9940a1187c2021-12-02T15:10:46ZNotch1 haploinsufficiency in mice accelerates adipogenesis10.1038/s41598-021-96017-z2045-2322https://doaj.org/article/1f7ab7957a43406f90deeb9940a1187c2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96017-zhttps://doaj.org/toc/2045-2322Abstract Notch signaling has been recognized recently as a key regulator of metabolism. Here, we determined the role of Notch1 in adipogenesis in wild-type (WT) and Notch1 hetero-mutant (N1+/−) mice provided with 12-week normal or high-fat diet. Haploinsufficiency of Notch1 was associated with adipose tissue accumulation despite similar food intake. White adipose tissue (WAT) of N1+/− showed accumulation of adipogenic cells (CD34+CD68+ cells), crown-like structures, and upregulation of cell proliferation markers (cyclin D1 and Ki67). Notch1 expression in WAT reached peak levels in 8-week-old WT mice in parallel with fat accumulation, especially under HF/HS-feeding, whereas such increment was blunted in N1+/− mice. Downstream of Notch1 haploinsufficiency, over-expression of adipogenic factors PPARγ and C/EBPα was noted following down-regulation of downstream transcriptional factors of Notch signaling (Hes-1, Pref-1, and Sox9). Both pharmacological Notch signal inhibition and Notch1 knockdown enhanced adipogenesis of 3T3-L1 preadipocytes. N1+/− mice showed impaired glucose and insulin tolerance with downregulation of IRS-1 and GLUT4 in WAT after high-fat diet. Taken together, our results suggest that haploinsufficiency of Notch1 promotes fat accumulation and adipogenesis and provides a mechanistic link between Notch signaling and development of metabolic syndrome.Kazutoshi YamaguchiMotoharu HayashiYasuhiro UchidaXian Wu ChengTakayuki NakayamaTadashi MatsushitaToyoaki MuroharaKyosuke TakeshitaNature 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 Kazutoshi Yamaguchi Motoharu Hayashi Yasuhiro Uchida Xian Wu Cheng Takayuki Nakayama Tadashi Matsushita Toyoaki Murohara Kyosuke Takeshita Notch1 haploinsufficiency in mice accelerates adipogenesis
description	Abstract Notch signaling has been recognized recently as a key regulator of metabolism. Here, we determined the role of Notch1 in adipogenesis in wild-type (WT) and Notch1 hetero-mutant (N1+/−) mice provided with 12-week normal or high-fat diet. Haploinsufficiency of Notch1 was associated with adipose tissue accumulation despite similar food intake. White adipose tissue (WAT) of N1+/− showed accumulation of adipogenic cells (CD34+CD68+ cells), crown-like structures, and upregulation of cell proliferation markers (cyclin D1 and Ki67). Notch1 expression in WAT reached peak levels in 8-week-old WT mice in parallel with fat accumulation, especially under HF/HS-feeding, whereas such increment was blunted in N1+/− mice. Downstream of Notch1 haploinsufficiency, over-expression of adipogenic factors PPARγ and C/EBPα was noted following down-regulation of downstream transcriptional factors of Notch signaling (Hes-1, Pref-1, and Sox9). Both pharmacological Notch signal inhibition and Notch1 knockdown enhanced adipogenesis of 3T3-L1 preadipocytes. N1+/− mice showed impaired glucose and insulin tolerance with downregulation of IRS-1 and GLUT4 in WAT after high-fat diet. Taken together, our results suggest that haploinsufficiency of Notch1 promotes fat accumulation and adipogenesis and provides a mechanistic link between Notch signaling and development of metabolic syndrome.
format	article
author	Kazutoshi Yamaguchi Motoharu Hayashi Yasuhiro Uchida Xian Wu Cheng Takayuki Nakayama Tadashi Matsushita Toyoaki Murohara Kyosuke Takeshita
author_facet	Kazutoshi Yamaguchi Motoharu Hayashi Yasuhiro Uchida Xian Wu Cheng Takayuki Nakayama Tadashi Matsushita Toyoaki Murohara Kyosuke Takeshita
author_sort	Kazutoshi Yamaguchi
title	Notch1 haploinsufficiency in mice accelerates adipogenesis
title_short	Notch1 haploinsufficiency in mice accelerates adipogenesis
title_full	Notch1 haploinsufficiency in mice accelerates adipogenesis
title_fullStr	Notch1 haploinsufficiency in mice accelerates adipogenesis
title_full_unstemmed	Notch1 haploinsufficiency in mice accelerates adipogenesis
title_sort	notch1 haploinsufficiency in mice accelerates adipogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1f7ab7957a43406f90deeb9940a1187c
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Notch1 haploinsufficiency in mice accelerates adipogenesis

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