Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring

Abstract We aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six w...

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Autores principales:	Takuya Kawamura, Hiroaki Tanaka, Ryota Tachibana, Kento Yoshikawa, Shintaro Maki, Kuniaki Toriyabe, Hiroki Takeuchi, Shinji Katsuragi, Kayo Tanaka, Tomoaki Ikeda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/172a576c50a747c98e5e559387bbb6ba
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spelling	oai:doaj.org-article:172a576c50a747c98e5e559387bbb6ba2021-12-02T15:22:59ZMaternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring10.1038/s41598-020-80643-02045-2322https://doaj.org/article/172a576c50a747c98e5e559387bbb6ba2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80643-0https://doaj.org/toc/2045-2322Abstract We aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.Takuya KawamuraHiroaki TanakaRyota TachibanaKento YoshikawaShintaro MakiKuniaki ToriyabeHiroki TakeuchiShinji KatsuragiKayo TanakaTomoaki IkedaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takuya Kawamura Hiroaki Tanaka Ryota Tachibana Kento Yoshikawa Shintaro Maki Kuniaki Toriyabe Hiroki Takeuchi Shinji Katsuragi Kayo Tanaka Tomoaki Ikeda Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring
description	Abstract We aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.
format	article
author	Takuya Kawamura Hiroaki Tanaka Ryota Tachibana Kento Yoshikawa Shintaro Maki Kuniaki Toriyabe Hiroki Takeuchi Shinji Katsuragi Kayo Tanaka Tomoaki Ikeda
author_facet	Takuya Kawamura Hiroaki Tanaka Ryota Tachibana Kento Yoshikawa Shintaro Maki Kuniaki Toriyabe Hiroki Takeuchi Shinji Katsuragi Kayo Tanaka Tomoaki Ikeda
author_sort	Takuya Kawamura
title	Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring
title_short	Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring
title_full	Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring
title_fullStr	Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring
title_full_unstemmed	Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring
title_sort	maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/172a576c50a747c98e5e559387bbb6ba
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Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring

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