Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy

Hypoglycemia resulting from a negative energy balance (NEB) in periparturient cattle is the major reason for a reduced glycogen content in polymorphonuclear neutrophils (PMNs). The lack of glycogen induces PMNs dysfunction and is responsible for the high incidence of perinatal diseases. The perinata...

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Autores principales:	Xinbo Wang, Yuming Zhang, Yansong Li, Mingyu Tang, Qinghua Deng, Jingdong Mao, Liyin Du
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	estrogen glucose metabolism autophagy ATP polymorphonuclear neutrophils cattle Veterinary medicine SF600-1100
Acceso en línea:	https://doaj.org/article/498d46781c5742e9a9b20aa4c821f281
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spelling	oai:doaj.org-article:498d46781c5742e9a9b20aa4c821f2812021-12-01T13:11:50ZEstrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy2297-176910.3389/fvets.2021.773514https://doaj.org/article/498d46781c5742e9a9b20aa4c821f2812021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fvets.2021.773514/fullhttps://doaj.org/toc/2297-1769Hypoglycemia resulting from a negative energy balance (NEB) in periparturient cattle is the major reason for a reduced glycogen content in polymorphonuclear neutrophils (PMNs). The lack of glycogen induces PMNs dysfunction and is responsible for the high incidence of perinatal diseases. The perinatal period is accompanied by dramatic changes in sex hormones levels of which estrogen (17β-estradiol, E2) has been shown to be closely associated with PMNs function. However, the precise regulatory mechanism of E2 on glucose metabolism in cattle PMNs has not been elucidated. Cattle PMNs were cultured in RPMI 1640 with 2.5 (LG), 5.5 (NG) and 25 (HG) mM glucose and E2 at 20 (EL), 200 (EM) and 450 (EH) pg/mL. We found that E2 maintained PMNs viability in different glucose conditions, and promoted glycogen synthesis by inhibiting PFK1, G6PDH and GSK-3β activity in LG while enhancing PFK1 and G6PDH activity and inhibiting GSK-3β activity in HG. E2 increased the ATP content in LG but decreased it in HG. This indicated that the E2-induced increase/decrease of ATP content may be independent of glycolysis and the pentose phosphate pathway (PPP). Further analysis showed that E2 promoted the activity of hexokinase (HK) and GLUT1, GLUT4 and SGLT1 expression in LG, while inhibiting GLUT1, GLUT4 and SGLT1 expression in HG. Finally, we found that E2 increased LC3, ATG5 and Beclin1 expression, inhibited p62 expression, promoting AMPK-dependent autophagy in LG, but with the opposite effect in HG. Moreover, E2 increased the Bcl-2/Bax ratio and decreased the apoptosis rate of PMNs in LG but had the opposite effect in HG. These results showed that E2 could promote AMPK-dependent autophagy and inhibit apoptosis in response to glucose-deficient environments. This study elucidated the detailed mechanism by which E2 promotes glycogen storage through enhancing glucose uptake and retarding glycolysis and the PPP in LG. Autophagy is essential for providing ATP to maintain the survival and immune potential of PMNs. These results provided significant evidence for further understanding the effects of E2 on PMNs immune potential during the hypoglycemia accompanying perinatal NEB in cattle.Xinbo WangYuming ZhangYansong LiMingyu TangQinghua DengJingdong MaoLiyin DuFrontiers Media S.A.articleestrogenglucose metabolismautophagyATPpolymorphonuclear neutrophilscattleVeterinary medicineSF600-1100ENFrontiers in Veterinary Science, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	estrogen glucose metabolism autophagy ATP polymorphonuclear neutrophils cattle Veterinary medicine SF600-1100
spellingShingle	estrogen glucose metabolism autophagy ATP polymorphonuclear neutrophils cattle Veterinary medicine SF600-1100 Xinbo Wang Yuming Zhang Yansong Li Mingyu Tang Qinghua Deng Jingdong Mao Liyin Du Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy
description	Hypoglycemia resulting from a negative energy balance (NEB) in periparturient cattle is the major reason for a reduced glycogen content in polymorphonuclear neutrophils (PMNs). The lack of glycogen induces PMNs dysfunction and is responsible for the high incidence of perinatal diseases. The perinatal period is accompanied by dramatic changes in sex hormones levels of which estrogen (17β-estradiol, E2) has been shown to be closely associated with PMNs function. However, the precise regulatory mechanism of E2 on glucose metabolism in cattle PMNs has not been elucidated. Cattle PMNs were cultured in RPMI 1640 with 2.5 (LG), 5.5 (NG) and 25 (HG) mM glucose and E2 at 20 (EL), 200 (EM) and 450 (EH) pg/mL. We found that E2 maintained PMNs viability in different glucose conditions, and promoted glycogen synthesis by inhibiting PFK1, G6PDH and GSK-3β activity in LG while enhancing PFK1 and G6PDH activity and inhibiting GSK-3β activity in HG. E2 increased the ATP content in LG but decreased it in HG. This indicated that the E2-induced increase/decrease of ATP content may be independent of glycolysis and the pentose phosphate pathway (PPP). Further analysis showed that E2 promoted the activity of hexokinase (HK) and GLUT1, GLUT4 and SGLT1 expression in LG, while inhibiting GLUT1, GLUT4 and SGLT1 expression in HG. Finally, we found that E2 increased LC3, ATG5 and Beclin1 expression, inhibited p62 expression, promoting AMPK-dependent autophagy in LG, but with the opposite effect in HG. Moreover, E2 increased the Bcl-2/Bax ratio and decreased the apoptosis rate of PMNs in LG but had the opposite effect in HG. These results showed that E2 could promote AMPK-dependent autophagy and inhibit apoptosis in response to glucose-deficient environments. This study elucidated the detailed mechanism by which E2 promotes glycogen storage through enhancing glucose uptake and retarding glycolysis and the PPP in LG. Autophagy is essential for providing ATP to maintain the survival and immune potential of PMNs. These results provided significant evidence for further understanding the effects of E2 on PMNs immune potential during the hypoglycemia accompanying perinatal NEB in cattle.
format	article
author	Xinbo Wang Yuming Zhang Yansong Li Mingyu Tang Qinghua Deng Jingdong Mao Liyin Du
author_facet	Xinbo Wang Yuming Zhang Yansong Li Mingyu Tang Qinghua Deng Jingdong Mao Liyin Du
author_sort	Xinbo Wang
title	Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy
title_short	Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy
title_full	Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy
title_fullStr	Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy
title_full_unstemmed	Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy
title_sort	estrogen regulates glucose metabolism in cattle neutrophils through autophagy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/498d46781c5742e9a9b20aa4c821f281
work_keys_str_mv	AT xinbowang estrogenregulatesglucosemetabolismincattleneutrophilsthroughautophagy AT yumingzhang estrogenregulatesglucosemetabolismincattleneutrophilsthroughautophagy AT yansongli estrogenregulatesglucosemetabolismincattleneutrophilsthroughautophagy AT mingyutang estrogenregulatesglucosemetabolismincattleneutrophilsthroughautophagy AT qinghuadeng estrogenregulatesglucosemetabolismincattleneutrophilsthroughautophagy AT jingdongmao estrogenregulatesglucosemetabolismincattleneutrophilsthroughautophagy AT liyindu estrogenregulatesglucosemetabolismincattleneutrophilsthroughautophagy
_version_	1718405170936676352

Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy

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