Background: Dexamethasone(Dex), a synthetic glucocorticoid, is among the most commonly used drugs worldwide in animals and humans as an anti-inflammatory and immunosuppressive agent. GC has profound effects on plasma ...Background: Dexamethasone(Dex), a synthetic glucocorticoid, is among the most commonly used drugs worldwide in animals and humans as an anti-inflammatory and immunosuppressive agent. GC has profound effects on plasma glucose level and other metabolic conditions. However, the effect of prolonged use of Dex on glucose metabolism in ruminants is still unclear.Results: Ten goats were randomly assigned to two groups: the control goats were injected with saline, and the Dex-treated goats were intramuscularly injected daily for 21 d with 0.2 mg/kg Dex. The results showed that plasma glucose and insulin concentrations were significantly increased after Dex administration(P < 0.05). Additionally, the content of hepatic glycogen was also markedly increased in Dex-treated goats(P < 0.01), while the content of glycogen in dorsal longissimus was unchanged by Dex(P > 0.05). The expression of several key genes, involved in blood glucose regulation, was detected by real-time PCR in the small intestine, skeletal muscle and liver. The expression of glucose transporter type 2(GLUT2), sodium-glucose transporter 1(SGLT1) and sodium-potassium ATPase(Na-K/ATPase) in the small intestine were generally increased by Dex, and GLUT2 m RNA expression was significantly up-regulated(P < 0.05). In liver, the expression of genes involved in gluconeogenesis including glucose-6-phosphatase catalytic subunit(G6 PC), cytosolic form of phosphoenolpyruvate carboxykinase(PCK1) and pyruvate carboxylase(PC), were significantly down-regulated by Dex. However, the protein expression levels of PCK1 & PCK2 were significantly increased by Dex, suggesting a post-transcriptional regulation. In dorsal longissimus, the m RNA expression of genes associated with gluconeogenesis and the insulin signaling pathway were generally upregulated by Dex, but the m RNA expression of two markers of muscle atrophy, namely F-box protein 32(FBXO32/Atrogin1) and muscle RING-finger protein 1(Mu RF1), was not altered by Dex.Conclusions: Taken together, these results indicate that chronic administration of a low dosage of Dex induces hyperglycemia mainly through gluconeogenesis activation in the goat liver.展开更多
Background： It is well known that feeding a high concentrate（HC） diet to lactating ruminants likely induces subacute ruminal acidosis（SARA） and leads to a decrease in milk fat production. However, the effects of ...Background： It is well known that feeding a high concentrate（HC） diet to lactating ruminants likely induces subacute ruminal acidosis（SARA） and leads to a decrease in milk fat production. However, the effects of feeding a HC diet for long periods on milk fatty acids composition and the mechanism behind the decline of milk fat still remains poorly understood. The aim of this study was to investigate the impact of feeding a HC diet to lactating dairy goats on milk fat yield and fatty acids composition with an emphasis on the mechanisms underlying the milk fat depression. Seventeen mid-lactating dairy goats were randomly allocated to three groups. The control treatment was fed a low-concentrate diet（35% concentrate, n = 5, LC） and there were two high-concentrate treatments（65% concentrate, HC）, one fed a high concentrate diet for a long period（19 wks, n = 7, HL）; one fed a high concentrate diet for a short period of time（4 wk, n = 5, HS）. Milk fat production and fatty acids profiles were measured. In order to investigate the mechanisms underlying the changes in milk fat production and composition,the gene expression involved in lipid metabolism and DNA methylation in the mammary gland were also analyzed.Results： Milk production was increased by feeding the HC diet in the HS and HL groups compared with the LC diet（P 〈 0.01）, while the percentage of milk fat was lower in the HL（P 〈 0.05） but not in the HS group. The total amount of saturated fatty acids（SFA） in the milk was not changed by feeding the HC diet, whereas the levels of unsaturated fatty acids（UFA） and monounsaturated fatty acids（MUFA） were markedly decreased in the HL group compared with the LC group（P 〈 0.05）. Among these fatty acids, the concentrations of C15：0（P 〈 0.01）, C17：0（P 〈 0.01）, C17：1（P 〈 0.01）, C18：1 n-9 c（P 〈 0.05）, C18：3 n-3 r（P 〈 0.01） and C20：0（P 〈 0.01） were markedly lower in the HL group, and the concentrations of C20：0（P 〈 0.05） and C18：3 n-3 r（P 〈 0.01） were lower in the HS group compared with the LC group. However, the concentrations of C18：2 n-6 c（P 〈 0.05） and C20：4 n-6（P 〈 0.05） in the milk fat were higher in the HS group. Real-time PCR results showed that the m RNA expression of the genes involved in milk fat production in the mammary gland was generally decreased in the HL and HS groups compared with the LC group. Among these genes, ACSL1, ACSS1 ＆ 2, ACACA, FAS, SCD, FADS2, and SREBP1 were downregulated in the mammary gland of the HL group（P 〈 0.05）, and the expressions of ACSS2, ACACA, and FADS2 m RNA were markedly decreased in the HS goats compared with the LC group（P 〈 0.05）. In contrast to the gene expression, the level of DNA methylation in the promoter regions of the ACACA and SCD genes was increased in the HL group compared with the LC group（P 〈 0.05）. The levels of ACSL1 protein expression and FAS enzyme activity were also decreased in the mammary gland of the HL compared with the LC group（P 〈 0.05）.Conclusions： Long-term feeding of a HC diet to lactating goats induced milk fat depression and FAs profile shift with lower MUFAs but higher SFAs. A general down-regulation of the gene expression involved in the milk fat production and a higher DNA methylation in the mammary gland may contribute to the decrease in milk fat production in goats fed a HC diet for long time periods.展开更多
基金supported by the National Nature Science Foundation of China(project no.31572433)the Program for New Century Excellent Talents in University(NCET-13-0862)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Background: Dexamethasone(Dex), a synthetic glucocorticoid, is among the most commonly used drugs worldwide in animals and humans as an anti-inflammatory and immunosuppressive agent. GC has profound effects on plasma glucose level and other metabolic conditions. However, the effect of prolonged use of Dex on glucose metabolism in ruminants is still unclear.Results: Ten goats were randomly assigned to two groups: the control goats were injected with saline, and the Dex-treated goats were intramuscularly injected daily for 21 d with 0.2 mg/kg Dex. The results showed that plasma glucose and insulin concentrations were significantly increased after Dex administration(P < 0.05). Additionally, the content of hepatic glycogen was also markedly increased in Dex-treated goats(P < 0.01), while the content of glycogen in dorsal longissimus was unchanged by Dex(P > 0.05). The expression of several key genes, involved in blood glucose regulation, was detected by real-time PCR in the small intestine, skeletal muscle and liver. The expression of glucose transporter type 2(GLUT2), sodium-glucose transporter 1(SGLT1) and sodium-potassium ATPase(Na-K/ATPase) in the small intestine were generally increased by Dex, and GLUT2 m RNA expression was significantly up-regulated(P < 0.05). In liver, the expression of genes involved in gluconeogenesis including glucose-6-phosphatase catalytic subunit(G6 PC), cytosolic form of phosphoenolpyruvate carboxykinase(PCK1) and pyruvate carboxylase(PC), were significantly down-regulated by Dex. However, the protein expression levels of PCK1 & PCK2 were significantly increased by Dex, suggesting a post-transcriptional regulation. In dorsal longissimus, the m RNA expression of genes associated with gluconeogenesis and the insulin signaling pathway were generally upregulated by Dex, but the m RNA expression of two markers of muscle atrophy, namely F-box protein 32(FBXO32/Atrogin1) and muscle RING-finger protein 1(Mu RF1), was not altered by Dex.Conclusions: Taken together, these results indicate that chronic administration of a low dosage of Dex induces hyperglycemia mainly through gluconeogenesis activation in the goat liver.
基金supported by the National Nature Science Foundation of China(project no.31572433)the National Key R&D Program(2016YFD0501203)+1 种基金the Program for New Century Excellent Talents in University(NCET-13-0862)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Background： It is well known that feeding a high concentrate（HC） diet to lactating ruminants likely induces subacute ruminal acidosis（SARA） and leads to a decrease in milk fat production. However, the effects of feeding a HC diet for long periods on milk fatty acids composition and the mechanism behind the decline of milk fat still remains poorly understood. The aim of this study was to investigate the impact of feeding a HC diet to lactating dairy goats on milk fat yield and fatty acids composition with an emphasis on the mechanisms underlying the milk fat depression. Seventeen mid-lactating dairy goats were randomly allocated to three groups. The control treatment was fed a low-concentrate diet（35% concentrate, n = 5, LC） and there were two high-concentrate treatments（65% concentrate, HC）, one fed a high concentrate diet for a long period（19 wks, n = 7, HL）; one fed a high concentrate diet for a short period of time（4 wk, n = 5, HS）. Milk fat production and fatty acids profiles were measured. In order to investigate the mechanisms underlying the changes in milk fat production and composition,the gene expression involved in lipid metabolism and DNA methylation in the mammary gland were also analyzed.Results： Milk production was increased by feeding the HC diet in the HS and HL groups compared with the LC diet（P 〈 0.01）, while the percentage of milk fat was lower in the HL（P 〈 0.05） but not in the HS group. The total amount of saturated fatty acids（SFA） in the milk was not changed by feeding the HC diet, whereas the levels of unsaturated fatty acids（UFA） and monounsaturated fatty acids（MUFA） were markedly decreased in the HL group compared with the LC group（P 〈 0.05）. Among these fatty acids, the concentrations of C15：0（P 〈 0.01）, C17：0（P 〈 0.01）, C17：1（P 〈 0.01）, C18：1 n-9 c（P 〈 0.05）, C18：3 n-3 r（P 〈 0.01） and C20：0（P 〈 0.01） were markedly lower in the HL group, and the concentrations of C20：0（P 〈 0.05） and C18：3 n-3 r（P 〈 0.01） were lower in the HS group compared with the LC group. However, the concentrations of C18：2 n-6 c（P 〈 0.05） and C20：4 n-6（P 〈 0.05） in the milk fat were higher in the HS group. Real-time PCR results showed that the m RNA expression of the genes involved in milk fat production in the mammary gland was generally decreased in the HL and HS groups compared with the LC group. Among these genes, ACSL1, ACSS1 ＆ 2, ACACA, FAS, SCD, FADS2, and SREBP1 were downregulated in the mammary gland of the HL group（P 〈 0.05）, and the expressions of ACSS2, ACACA, and FADS2 m RNA were markedly decreased in the HS goats compared with the LC group（P 〈 0.05）. In contrast to the gene expression, the level of DNA methylation in the promoter regions of the ACACA and SCD genes was increased in the HL group compared with the LC group（P 〈 0.05）. The levels of ACSL1 protein expression and FAS enzyme activity were also decreased in the mammary gland of the HL compared with the LC group（P 〈 0.05）.Conclusions： Long-term feeding of a HC diet to lactating goats induced milk fat depression and FAs profile shift with lower MUFAs but higher SFAs. A general down-regulation of the gene expression involved in the milk fat production and a higher DNA methylation in the mammary gland may contribute to the decrease in milk fat production in goats fed a HC diet for long time periods.
