Hepatic glycogenolysis is determined by maternal high-calorie diet via methylation of Pygl and it is modified by oteocalcin administration in mice

Objective: Accumulating evidence indicates that an adverse perinatal environment contributes to a higher risk of metabolic disorders in the later life of the offspring. However, the underlying molecular mechanisms remain largely unknown. Thus, we investigated the contribution of maternal high-calori...

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Autores principales:	Tomoyo Kawakubo-Yasukochi, Ena Yano, Soi Kimura, Takuya Nishinakagawa, Akiko Mizokami, Yoshikazu Hayashi, Yuji Hatakeyama, Kenji Ohe, Atsushi Yasukochi, Seiji Nakamura, Eijiro Jimi, Masato Hirata
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Pygl Ahr Glycogen DNA methylation Osteocalcin Developmental origins of health and disease Internal medicine RC31-1245
Acceso en línea:	https://doaj.org/article/654097220e7d4bd0b52f2707bfd75b06
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spelling	oai:doaj.org-article:654097220e7d4bd0b52f2707bfd75b062021-11-20T05:05:53ZHepatic glycogenolysis is determined by maternal high-calorie diet via methylation of Pygl and it is modified by oteocalcin administration in mice2212-877810.1016/j.molmet.2021.101360https://doaj.org/article/654097220e7d4bd0b52f2707bfd75b062021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2212877821002076https://doaj.org/toc/2212-8778Objective: Accumulating evidence indicates that an adverse perinatal environment contributes to a higher risk of metabolic disorders in the later life of the offspring. However, the underlying molecular mechanisms remain largely unknown. Thus, we investigated the contribution of maternal high-calorie diet and osteocalcin to metabolic homeostasis in the offspring. Methods: Eight-week-old C57Bl/6N female mice were mated with age-matched males and allocated randomly to three groups: a normal-diet (ND) or a high-fat, high-sucrose diet group, which was administered either saline (control) or GluOC (10 ng/g body mass) from the day of mating to that of delivery, and the dams were fed a ND after the delivery. Pups weaned at 24 days after birth were analyzed. Results: A maternal high-fat, high-sucrose diet during pregnancy causes metabolic disorders in the liver of the offspring via hypermethylation of the Pygl gene, encoding glycogen phosphorylase L, which mediates hepatic glycogenolysis. The reduced expression of Pygl induced by the maternal diet causes the hepatic accumulation of glycogen and triglyceride in the offspring, which remains in adulthood. In addition, the administration of uncarboxylated osteocalcin during pregnancy upregulates Pygl expression via both direct CREBH and ATF4 and indirect epigenomic pathways, mitigating the maternal diet-induced obesity and abnormal glucose and lipid metabolism in adulthood. Conclusions: We propose that maternal energy status is reflected in the hepatic glycogenolysis capacity of the offspring via epigenetic modification of Pygl and uncarboxylated osteocalcin regulates glycogenolysis.Tomoyo Kawakubo-YasukochiEna YanoSoi KimuraTakuya NishinakagawaAkiko MizokamiYoshikazu HayashiYuji HatakeyamaKenji OheAtsushi YasukochiSeiji NakamuraEijiro JimiMasato HirataElsevierarticlePyglAhrGlycogenDNA methylationOsteocalcinDevelopmental origins of health and diseaseInternal medicineRC31-1245ENMolecular Metabolism, Vol 54, Iss , Pp 101360- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pygl Ahr Glycogen DNA methylation Osteocalcin Developmental origins of health and disease Internal medicine RC31-1245
spellingShingle	Pygl Ahr Glycogen DNA methylation Osteocalcin Developmental origins of health and disease Internal medicine RC31-1245 Tomoyo Kawakubo-Yasukochi Ena Yano Soi Kimura Takuya Nishinakagawa Akiko Mizokami Yoshikazu Hayashi Yuji Hatakeyama Kenji Ohe Atsushi Yasukochi Seiji Nakamura Eijiro Jimi Masato Hirata Hepatic glycogenolysis is determined by maternal high-calorie diet via methylation of Pygl and it is modified by oteocalcin administration in mice
description	Objective: Accumulating evidence indicates that an adverse perinatal environment contributes to a higher risk of metabolic disorders in the later life of the offspring. However, the underlying molecular mechanisms remain largely unknown. Thus, we investigated the contribution of maternal high-calorie diet and osteocalcin to metabolic homeostasis in the offspring. Methods: Eight-week-old C57Bl/6N female mice were mated with age-matched males and allocated randomly to three groups: a normal-diet (ND) or a high-fat, high-sucrose diet group, which was administered either saline (control) or GluOC (10 ng/g body mass) from the day of mating to that of delivery, and the dams were fed a ND after the delivery. Pups weaned at 24 days after birth were analyzed. Results: A maternal high-fat, high-sucrose diet during pregnancy causes metabolic disorders in the liver of the offspring via hypermethylation of the Pygl gene, encoding glycogen phosphorylase L, which mediates hepatic glycogenolysis. The reduced expression of Pygl induced by the maternal diet causes the hepatic accumulation of glycogen and triglyceride in the offspring, which remains in adulthood. In addition, the administration of uncarboxylated osteocalcin during pregnancy upregulates Pygl expression via both direct CREBH and ATF4 and indirect epigenomic pathways, mitigating the maternal diet-induced obesity and abnormal glucose and lipid metabolism in adulthood. Conclusions: We propose that maternal energy status is reflected in the hepatic glycogenolysis capacity of the offspring via epigenetic modification of Pygl and uncarboxylated osteocalcin regulates glycogenolysis.
format	article
author	Tomoyo Kawakubo-Yasukochi Ena Yano Soi Kimura Takuya Nishinakagawa Akiko Mizokami Yoshikazu Hayashi Yuji Hatakeyama Kenji Ohe Atsushi Yasukochi Seiji Nakamura Eijiro Jimi Masato Hirata
author_facet	Tomoyo Kawakubo-Yasukochi Ena Yano Soi Kimura Takuya Nishinakagawa Akiko Mizokami Yoshikazu Hayashi Yuji Hatakeyama Kenji Ohe Atsushi Yasukochi Seiji Nakamura Eijiro Jimi Masato Hirata
author_sort	Tomoyo Kawakubo-Yasukochi
title	Hepatic glycogenolysis is determined by maternal high-calorie diet via methylation of Pygl and it is modified by oteocalcin administration in mice
title_short	Hepatic glycogenolysis is determined by maternal high-calorie diet via methylation of Pygl and it is modified by oteocalcin administration in mice
title_full	Hepatic glycogenolysis is determined by maternal high-calorie diet via methylation of Pygl and it is modified by oteocalcin administration in mice
title_fullStr	Hepatic glycogenolysis is determined by maternal high-calorie diet via methylation of Pygl and it is modified by oteocalcin administration in mice
title_full_unstemmed	Hepatic glycogenolysis is determined by maternal high-calorie diet via methylation of Pygl and it is modified by oteocalcin administration in mice
title_sort	hepatic glycogenolysis is determined by maternal high-calorie diet via methylation of pygl and it is modified by oteocalcin administration in mice
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/654097220e7d4bd0b52f2707bfd75b06
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Hepatic glycogenolysis is determined by maternal high-calorie diet via methylation of Pygl and it is modified by oteocalcin administration in mice

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