Mechanisms of Hepatic Gluconeogenesis and Nutritional Regulation in Ruminants

ZHU Wen; REN Chunhuan; ZHANG Yan; ZHANG Zijun

doi:10.3969/j.issn.1006-267x.2019.10.004

Chinese Journal of Animal Nutrition >

2019 , Vol. 31 >Issue 10: 4434 - 4441

DOI: https://doi.org/10.3969/j.issn.1006-267x.2019.10.004

Mechanisms of Hepatic Gluconeogenesis and Nutritional Regulation in Ruminants

ZHU Wen ,
REN Chunhuan ,
ZHANG Yan ,
ZHANG Zijun

Expand

College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China

Received date: 2019-03-29

Online published: 2019-10-17

Fold

Abstract

Glucose is the main energy substrate, which plays an important role in mammalian metabolism. Ruminants have a large reliance on gluconeogenesis in terms of meeting the glucose requirement, and liver comprises mainly of the total gluconeogenesis capacity. Important pathways/signal factors including phosphatidylinositol 3 kinase/protein kinase B-forkhead box protein O1(PI3K/Akt-FoxO1), AMP-activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR) are closely related to the hepatic gluconeogenesis, and nutrition substrates, enzyme activity, and hormone play an important role in regulation of hepatic gluconeogenesis in ruminants. Therefore, the mechanism of hepatic gluconeogenesis as well as the influence of nutritional regulations were summarized in this article, in order to provide the basic knowledge and reference for improvement of ruminant health, growth and production performance.

Key words： gluconeogenesis; gene expression; enzyme activity; nutritional regulation; ruminant; liver

Cite this article

ZHU Wen , REN Chunhuan , ZHANG Yan , ZHANG Zijun . Mechanisms of Hepatic Gluconeogenesis and Nutritional Regulation in Ruminants[J]. Chinese Journal of Animal Nutrition, 2019 , 31(10) : 4434 -4441 . DOI: 10.3969/j.issn.1006-267x.2019.10.004

References

[1] CÁRDENAS M L,CORNISH-BOWDEN A,URETA T.Evolution and regulatory role of the hexokinases[J].Biochimica et Biophysica Acta:Molecular Cell Research,1998,1401(3):242-264.

[2] CANKAYA M,HERNANDEZ A M,CIFTCI M,et al.An analysis of expression patterns of genes encoding proteins with catalytic activities[J].BMC Genomics,2007,8:232.
[3] MAYES P A,BENDER D A.Gluconeogenesis and control of blood glucose[M]//MURRAY R K,GRANNER D K,MAYES P A,et al.Harper's biochemistry.24th ed.Stamford,CT:Appleton & Lange,1996:194-204.
[4] ASCHENBACH J R,KRISTENSEN N B,DONKIN S S,et al.Gluconeogenesis in dairy cows:the secret of making sweet milk from sour dough[J].IUBMB Life,2010,62(12):869-877.

[5] GRUMMER R R.Impact of changes in organic nutrient metabolism on feeding the transition dairy cow[J].Journal of Animal Science,1995,73(9):2820-2833.

[6] BERGMAN E N.Glucose metabolism in ruminants as related to hypoglycemia and ketosis[J].Cornell Veterinarian,1973,63(3):341-382.
[7] KARCHER E L,PICKETT M M,VARGA G A,et al.Effect of dietary carbohydrate and monensin on expression of gluconeogenic enzymes in liver of transition dairy cows[J].Journal of Animal Science,2007,85(3):690-699.

[8] ARMENTANO L E.Ruminant hepatic metabolism of volatile fatty acids,lactate and pyruvate[J].The Journal of Nutrition,1992,122(Suppl.3):838-842.
[9] AGCA C,GREENFIELD R B,HARTWELL J R,et al.Cloning and characterization of bovine cytosolic and mitochondrial PEPCK during transition to lactation[J].Physiological Genomics,2002,11(2):53-63.

[10] 邢燕,关育红,张金,等.肝脏组织磷脂酰肌醇3-激酶/蛋白激酶B信号通路参与降低胎儿生长受限大鼠的胰岛素敏感性[J].中华围产医学杂志,2012,15(12):743-749.
[11] CARTER M E,BRUNET A.FoxO transcription factors[J].Current Biology,2007,17(4):R113-R114.
[12] ZHANG W W,PATIL S,CHAUHAN B,et al.FoxO1 regulates multiple metabolic pathways in the liver:effects on gluconeogenic,glycolytic,and lipogenic gene expression[J].The Journal of Biological Chemistry,2006,281(15):10105-10117.

[13] KAMAGATE A,KIM D H,ZHANG T,et al.FoxO1 links hepatic insulin action to endoplasmic reticulum stress[J].Endocrinology,2010,151(8):3521-3535.

[14] CHOI S,YOON H,OH K S,et al.Widespread effects of nicotinic acid on gene expression in insulin-sensitive tissues:implications for unwanted effects of nicotinic acid treatment[J].Metabolism,2011,60(1):134-144.

[15] GOYAL N,TIWARY S,KESHARWANI D,et al.Long non-coding RNA H19 inhibition promotes hyperglycemia in mice by upregulating hepatic FoxO1 levels and promoting gluconeogenesis[J].Journal of Molecular Medicine,2019,97(1):115-126.

[16] TSUZUKI K,ITOH Y,INOUE Y,et al.TRB1 negatively regulates gluconeogenesis by suppressing the transcriptional activity of FoxO1[J].FEBS Letters,2019,593(3):369-380.

[17] CATON P W,NAYUNI N K,KIESWICH J,et al.Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5[J].Journal of Endocrinology,2010,205(1):97-106.

[18] DASHTY M.A quick look at biochemistry:carbohydrate metabolism[J].Clinical Biochemistry,2013,46(15):1339-1352.

[19] CHI Y J,MENG Y H,WANG J P,et al.FAM3B (PANDER) functions as a co-activator of FOXO1 to promote gluconeogenesis in hepatocytes[J].Journal of Cellular and Molecular Medicine,2019,23(3):1746-1758.

[20] THORN S R,SEKAR S M,LAVEZZI J R,et al.A physiological increase in insulin suppresses gluconeogenic gene activation in fetal sheep with sustained hypoglycemia[J].American Journal of Physiology:Regulatory,Integrative and Comparative Physiology,2012,303(8):R861-R869.
[21] GRALA T M,KAY J K,PHYN C V C,et al.Reducing milking frequency during nutrient restriction has no effect on the hepatic transcriptome of lactating dairy cattle[J].Physiological Genomics,2013,45(23):1157-1167.

[22] KINOSHITA A,LOCHER L,TIENKEN R,et al.Associations between Forkhead Box O1(FoxO1) expression and indicators of hepatic glucose production in transition dairy cows supplemented with dietary nicotinic acid[J].PLoS One,2016,11(1):e0146670.
[23] KIM Y D,PARK K G,LEE Y S,et al.Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP[J].Diabetes,2008,57(2):306-314.

[24] CARLING D.The AMP-activated protein kinase cascade-a unifying system for energy control[J].Trends in Biochemical Sciences,2004,29(1):18-24.

[25] JIANG S J,DONG H,LI J B,et al.Berberine inhibits hepatic gluconeogenesis via the LKB1-AMPK-TORC2 signaling pathway in streptozotocin-induced diabetic rats[J].World Journal of Gastroenterology,2015,21(25):7777-7785.

[26] CHUNG H T.SHP gains citizenship of the AMPK kingdom[J].Cellular and Molecular Immunology,2011,8(6):450-452.

[27] SHAW R J,LAMIA K A,VASQUEZ D,et al.The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin[J].Science,2005,310(5754):1642-1646.

[28] CHEN H,ZHANG L,LI X W,et al.Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes[J].The Journal of Steroid Biochemistry and Molecular Biology,2013,138:445-454.
[29] BROWN L D,KOHN J R,ROZANCE P J,et al.Exogenous amino acids suppress glucose oxidation and potentiate hepatic glucose production in late gestation fetal sheep[J].American Journal of Physiology:Regulatory,Integrative and Comparative Physiology,2017,312(5):R654-R663.
[30] STADLBAUER K,BRUNMAIR B,SZÖCS Z,et al.The effects of amino acids on glucose metabolism of isolated rat skeletal muscle are independent of insulin and the mTOR/S6K pathway[J].American Journal of Physiology-Endocrinology and Metabolism,2009,297(3):E785-E792.
[31] LAPLANTE M,SABATINI D M.mTORC1 activates SREBP-1c and uncouples lipogenesis from gluconeogenesis[J].Proceedings of the National Academy of Sciences of the United States of America,2010,107(8):3281-3282.

[32] SABATINI D M.Twenty-five years of mTOR:uncovering the link from nutrients to growth[J].Proceedings of the National Academy of Sciences of the United States of America,2017,114(45):11818-11825.

[33] CASTELLANO B M,THELEN A M,MOLDAVSKI O,et al.Lysosomal cholesterol activates mTORC1 via an SLC38A9-niemann-pick C1 signaling complex[J].Science,2017,355(6331):1306-1311.

[34] XU T,ALHARTHI A S M,BATISTEL F,et al.Hepatic phosphorylation status of serine/threonine kinase 1,mammalian target of rapamycin signaling proteins,and growth rate in Holstein heifer calves in response to maternal supply of methionine[J].Journal of Dairy Science,2018,101(9):8476-8491.

[35] ZHENG C,YAO J H,GUO L,et al.Leucine-induced promotion of post-absorptive EAA utilization and hepatic gluconeogenesis contributes to protein synthesis in skeletal muscle of dairy calves[J].Journal of Animal Physiology and Animal Nutrition,2019,103(3):705-712.

[36] LARSEN M,KRISTENSEN N B.Precursors for liver gluconeogenesis in periparturient dairy cows[J].Animal,2013,7(10):1640-1650.

[37] OBA M,ALLEN M S.Extent of hypophagia caused by propionate infusion is related to plasma glucose concentration in lactating dairy cows[J].The Journal of Nutrition,2003,133(4):1105-1112.

[38] 刘威.丙酸对山羊血液理化指标、真胃组织结构及相关基因表达的影响[D].硕士学位论文.扬州:扬州大学,2016.
[39] ZHANG Q,KOSER S L,BEQUETTE B J,et al.Effect of propionate on mRNA expression of key genes for gluconeogenesis in liver of dairy cattle[J].Journal of Dairy Science,2015,98(12):8698-8709.

[40] ZHANG Q,KOSER S L,DONKIN S S.Propionate induces mRNA expression of gluconeogenic genes in bovine calf hepatocytes[J].Journal of Dairy Science,2016,99(5):3908-3915.

[41] BOUGOUIN A,FERLAY A,DOREAU M,et al.Effects of carbohydrate type or bicarbonate addition to grass silage-based diets on enteric methane emissions and milk fatty acid composition in dairy cows[J].Journal of Dairy Science,2018,101(7):6085-6097.

[42] CASTRO-MONTOYA J,WITZIG M,RAHMAN M,et al.In vitro rumen fermentation,microbial protein synthesis and composition of microbial community of total mixed rations replacing maize silage with red clover silage[J].Journal of Animal Physiology and Animal Nutrition,2018,102(6):1450-1463.

[43] WANG B,MAO S Y,YANG H J,et al.Effects of alfalfa and cereal straw as a forage source on nutrient digestibility and lactation performance in lactating dairy cows[J].Journal of Dairy Science,2014,97(12):7706-7715.

[44] MARKANTONATOS X,VARGA G A.Effects of monensin on glucose metabolism in transition dairy cows[J].Journal of Dairy Science,2017,100(11):9020-9035.

[45] KHIAOSA-ARD R,ZEBELI Q.Meta-analysis of the effects of essential oils and their bioactive compounds on rumen fermentation characteristics and feed efficiency in ruminants[J].Journal of Animal Science,2013,91(4):1819-1830.

[46] PRIOR R L,SCOTT R A.Ontogeny of gluconeogenesis in the bovine fetus:influence of maternal dietary energy[J].Developmental Biology,1977,58(2):384-393.

[47] 冯仰廉.反刍动物营养学[M].北京:科学出版社,2004:509-510.
[48] WALDROP G L,HOLDEN H M,ST. MAURICE M.The enzymes of biotin dependent CO₂ metabolism:what structures reveal about their reaction mechanisms[J].Protein Science,2012,21(11):1597-1619.

[49] PETERS J P,ELLIOT J M.Effect of vitamin B₁₂ status on performance of the lactating ewe and gluconeogenesis from propionate[J].Journal of Dairy Science,1983,66(9):1917-1925.

[50] ROLLIN E,BERGHAUS R D,RAPNICKI P,et al.The effect of injectable butaphosphan and cyanocobalamin on postpartum serum β-hydroxybutyrate,calcium,and phosphorus concentrations in dairy cattle[J].Journal of Dairy Science,2010,93(3):978-987.

[51] ZIMMERLY C A,WEISS W P.Effects of supplemental dietary biotin on performance of Holstein cows during early lactation[J].Journal of Dairy Science,2001,84(2):498-506.

[52] HAUSMANN J,DEINER C,IMMIG I,et al.Effects of combined supplementation with plant bioactive lipid compounds and biotin on ruminal fermentation,body condition and energy metabolism in transition dairy cows[J].Animal Feed Science and Technology,2017,225:27-37.
[53] WANG D M,ZHANG B X,WANG J K,et al.Effect of dietary supplements of biotin,intramuscular injections of vitamin B₁₂,or both on postpartum lactation performance in multiparous dairy cows[J].Journal of Dairy Science,2018,101(9):7851-7856.

[54] 王炳.饲喂秸秆日粮奶牛泌乳性能低下的消化吸收与代谢机制研究[D].博士学位论文.杭州:浙江大学,2016.
[55] 茹婷.基于p53-SIRT6-Fox01轴下烟酸对围产期绵羊肝脏糖异生作用的影响研究[D].硕士学位论文.呼和浩特:内蒙古农业大学,2018:4.
[56] WHITE H M,CARVALHO E R,KOSER S L,et al.Short communication:regulation of hepatic gluconeogenic enzymes by dietary glycerol in transition dairy cows[J].Journal of Dairy Science,2016,99(1):812-817.

[57] 李红梅.干奶期不同能量摄食对奶牛糖异生的影响[D].硕士学位论文.哈尔滨:东北农业大学,2006.

Options

Outlines

模态框（Modal）标题

Abstract

Cite this article

References