Subscribe to RSS
DOI: 10.1055/a-2066-2596
Die Leberverfettung der Milchkuh: Teil 1
Bedeutung von Insulin und der Wachstumshormon-IGF-1-AchseThe lipidosis of the liver of dairy cows: Part 1Role of insulin and the Growth Hormone-IGF-1 axisZusammenfassung
Die Fettleber von Milchkühen ist seit vielen Jahren bekannt und bedingt durch eine vermehrte Aufnahme von freien Fettsäuren (NEFA) in die Leberzellen und unzureichender Metabolisierung in Relation zur Abgabe der NEFA als resynthetisierte Triglyzeride (TG). Die Pathogenese der Fettleber umfasst a) eine erhöhte Lipolyse im Fettgewebe mit einem Anstieg der freien Fettsäuren (NEFA) Konzentration im Blut, b) die Aufnahme von NEFA in die Leberzellen proportional der Konzentration, c) die Metabolisierung der NEFA (Oxidation, Bildung von Ketonkörpern), d) die erneute Synthese von TG bzw. von very low density lipoprotein (VLDL) und e) deren Abgabe. An diesen Schritten (a–e) sind hormonelle Veränderungen maßgeblich beteiligt. Es handelt sich um den Anstieg des Wachstumshormons (GH), eine ausgeprägte Insulinresistenz in Verbindung mit einem Abfall der Insulin- und IGF-1-Konzentration im Blut. Als Folge dieser hormonellen Veränderungen ergibt sich mit steigender Milchleistung eine Entkoppelung der GH-IGF-1-Achse in der Leber mit einer vermehrten Lipolyse im Fettgewebe, Freisetzung von NEFA und den o.a. Konsequenzen. Diese Veränderungen sind assoziiert mit Entzündungserscheinungen, oxidativen und endoplasmatischen Stress. Die hormonellen Veränderungen mit den metabolischen Konsequenzen sind das Ergebnis der primären Selektion auf hohe Milchleistung ohne bedarfsgerechte Futteraufnahme und als Ursache der Pathogenese der Leberverfettung und Ketose und deren Folgeerkrankungen („Produktionskrankheiten“) anzusehen.
Abstract
Lipidosis of the liver of dairy cows is a metabolic disease known since many years and is caused by an uptake of nonesterified fatty acids (NEFA) into the liver cells, limited metabolism of NEFA (oxidation and production of β-hydroxybutyrate), and resynthesis in relation to a low efflux as triglyceride (TG). The pathogenesis of lipidosis includes a) an augmented release of NEFA by mobilisation of adipose tissue, b) uptake of NEFA into the liver cells, c) metabolism of NEFA and d) re-synthesis of triglyceride and e) an efflux of TG as very low density lipoprotein (VLDL). The steps a–e are postpartum modified by hormones as an increase of growth hormone, a pronounced insulin resistance in combination with a decreased insulin and of IGF-1 concentrations. These hormonal changes are related to an uncoupling of the growth hormone-IGF-1-axis with enhanced lipolysis and consequences mentioned above. These alterations are associated with inflammation, oxidative and endoplasmatic stress. The metabolic and hormonal alterations are the result of the selection of dairy cows primarily for milk production without adequate food intake with the consequence of lipidosis, ketosis and further health risks (production diseases).
Publication History
Received: 16 August 2022
Accepted: 27 March 2023
Article published online:
25 May 2023
© 2023. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
Literatur
- 1 Reid I.. Incidence and severity of fatty liver in dairy cows. Vet Rec 1980; 197: 281-284 DOI: 10.1136/yr107.12.281.
- 2 Fürll M.. Vorkommen, Ätiologie, Pathogenese, Diagnostik und medizinische Beeinflussung von Leberschäden beim Rind. Habilitationsschrift. 1989 Universität Leipzig
- 3 Danfær V.. Nutrient metabolism and utilization in the liver. Livestock Prod. Sci 1994; 39: 115-127 DOI: 10.1016/0301-6226(94)90163-5.
- 4 Herdt T.. Ruminant adaptation to negative energy balance. Influences on the aetiology of ketosis and fat liver. Vet. Clin. North America: Food Animal Pract 2000; 16: 215-230 DOI: 10.1016/S0749-0720(15)30102-X.
- 5 Geelen M, Wensing T.. Studies on hepatic lipidosis and coinciding health and fertility problems of high-producing dairy cows using the “Utrecht fatty liver model of dairy cows”. A Review. Veterinary Quarterly 2006; 28: 90-104 DOI: 10.1080/01652176.2006.9695214.
- 6 Bobe G, Young J, Beitz D.. Invited review: Pathology, aetiology, prevention, and treatment of fat liver in dairy cows. J Dairy Sci 2004; 87: 3105-3124 DOI: 10.3168/jds.S0022-0302(04)73446-3.
- 7 Pietsch F, Schären M, Snedec T. et al. Aspects of transition cow metabolomics—Part II: Histomorphologic changes in the liver parenchyma throughout the transition period, in cows with different liver metabotypes and effects of a metaphylactic butaphosphan and cyanocobalamin treatment. J Dairy Sci 2021; 104: 9227-9244 DOI: 10.3168/jds.2020-19057.
- 8 Rukkwamsuk T, Wensing T, Geelen M.. Effect of overfeeding during the dry period on the rate of esterification in adipose tissue of dairy cows during the periparturient period. J Dairy Sci 1998; 81: 2904-2911 DOI: 10.3168/jds.S0022-0302(98)75851-5.
- 9 Bollatti J, Zenobi M, Barton B. et al. Responses to rumen-protected choline in transition cows do not depend on prepartum body condition. J Dairy Sci 2020; 103: 2272-2286 DOI: 10.3168/jds.2019-17302.
- 10 De Koster J, Hostens M, Van Eetvelde M. et al. Insulin response of the glucose and fatty acid metabolism in dry dairy cows across a range of body condition scores. J Dairy Sci 2015; 98: 4580-4592 DOI: 10.3168/jds.2015-9341.
- 11 Arshad K, Santos J.. Hepatic triacylglycerol associations with production and health in dairy cows. J Dairy Sci 2022; 105: 5393-5409 DOI: 10.3168/jds.2021-21031.
- 12 Zenobi M, Scheffler T, Zuniga J. et al. Feeding increasing amounts of ruminally protected choline decreased fatty liver in non-lactating, pregnant Holstein cows in negative energy status. J Dairy Sci 2018; 101: 5902-5923 DOI: 10.3168/jds.2017-13973.
- 13 Vernon R.. Lipid metabolism during lactation: A review of adipose tissue-liver interactions and the development of fatty liver. J Dairy Res 2005; 72: 460-469 DOI: 10.1017/S0022029905001299.
- 14 Gaal T, Reid M, Collins R. et al. Comparison of biochemical and histological methods of estimating fat content of liver of dairy cows. Res. Vet. Sci. 1983; 34: 254-248 DOI: 10.1016/S0034-5288(18)32268-9.
- 15 Katoh N.. Relevance of apolipoproteins in the development of fat liver and fat liver-related peripartum diseases in dairy cows. J Vet Med Sci 2002; 64: 293-307 DOI: 10.1292/jvms.64.293.
- 16 GfE (Gesellschaft für Ernährungsphysiologie) In G. Flachowsky, H. Jeroch, M. Kirchgeßner, et al. (Eds.). Empfehlungen zur Energie- und Nährstoffversorgung der Milchkühe und Aufzuchtrinder. DLG Verlag Frankfurt 2001, Germany
- 17 Vernon R.. Homeorhesis pp. 64-73. Year Book Hannah Research Institute. 1998
- 18 Martens H.. Transition period of the dairy cow revisited: I. Homeorhesis and its changes by selection and management. J Agric Sci 2020A 12: 1-24 DOI: 10.5539/jas.v12n3p1.
- 19 Karacaören B, Jaffrézi F, Kadarmideen H.. Genetic parameters for functional traits in dairy cattle from random regression models. J Dairy Sci 2006; 89: 791-798 DOI: 10.3168/jds.S0022-0302(06)72141-5.
- 20 Liinamo A, Mäntysaari P, Mäntysaari E.. Short communication: energetic parameters for feed intake, production, and extent of negative energy balance in Nordic Red dairy cattle. J Dairy Sci 2012; 95: 6788-6794 DOI: 10.3168/jds.2012-5342.
- 21 Manzanilla-Pech M, Veerkamp R, Calus M. et al. Genetic parameters across lactation for feed intake, fat- and protein-corrected milk, and live weight in first-parity Holstein cattle. J Dairy Sci 2014; 97: 5851-5862 DOI: 10.3168/jds.2014-8165.
- 22 Krattenmacher N, Thaller G, Tetens J.. Analysis of the genetic architecture of energy balance and its major determinants dry matter intake and energy-corrected milk yield in primiparous Holstein cows. J Dairy Sci 2019; 102: 3241-3253 DOI: 10.3168/jds.2018-15480.
- 23 Gruber L, Pries M, Schwarz F.-J. et al. DLG-Information 2006; 2-29 Retrieved from http://www.dlg.org/fachinfos-rinder.htm
- 24 Buttchereit N, Stamer E, Junge W. et al. Short communication: Genetic relationship among daily energy balance, feed intake, body condition score, and fat to protein ratio of milk in dairy cows. J Dairy Sci 2011; 94: 1586-1591 DOI: 10.3168/jds.2010-3396.
- 25 Bar-Peled U, Aharoni Y, Robinson B. et al. The effect of enhanced milk yield of dairy cows by frequent milking or suckling on intake and digestibility of the diet. J Dairy Sci 1998; 81: 1420-1427 DOI: 10.3168/jds.S0022-0302(98)75706-6.
- 26 Okamura C, Bader J, Keisler D. et al. Short communication: Growth hormone receptor expression in two dairy breeds during the periparturient period. J Dairy Sci 2009; 92: 2706-2710 DOI: 10.3168/jds.2008-1775.
- 27 Jiang H, Lucy M, Crooker B. et al. Expression of growth hormone Receptor 1A mRNA is decreased in dairy cows but not in beef cows at parturition. J Dairy Sci 2005; 88: 1370-1377 DOI: 10.3168/jds.S0022-0302(05)72804-6.
- 28 Lucy M.. Functional differences in growth hormone and insulin-like growth factor axis in cattle and pigs: Implications for post-partum nutrition and reproduction. Reprod. Domest. Anim 2008; 43: 31-39 DOI: 10.1111/j.1439-0531.2008.01140.x.
- 29 McNamara J.. Integrating genotype and nutrition on utilization of body reserves during lactation of dairy cattle. 2000: 353-370 in Symposium on Ruminant Physiology. P. B. Cronje, ed.CAB Int. London, UK
- 30 Roberts C, Reid I, Roelands G. et al. A fat mobilisation syndrome in dairy cows in early lactation. Vet. Rec. 1981; 108: 7-9 DOI: 10.1136/vr.108.1.7.
- 31 Reid I, Roberts J.. Fat liver in dairy cows. Practice 1982; 11: 164-169 DOI: 10.1136/inpract.4.6.164.
- 32 Hocquette J, Bauchart D.. Intestinal absorption, blood transport and hepatic and muscle metabolism of fatty acids in preruminant and ruminant animals. Reprod. Nutr. Develop. 1999; 39: 27-48
- 33 Reynolds C, Aikman P, Lupoli B. et al. Splanchnic metabolism of dairy cows through transition from late gestation through early lactation. J Dairy Sci 2003; 86: 1201-1217 DOI: 10.3168/jds.S0022-0302(03)73704-7.
- 34 Chamberlin W, Middleton J, Spain J. et al. Subclinical hypocalcemia, plasma biochemical parameters, lipid metabolism, postpartum disease, and fertility in postparturient dairy cows. J Dairy Sci 2013; 96: 7001-7013 DOI: 10.3168/jds.2013-6901.
- 35 White H.. The role of TCA cycle in ketosis and fat liver in periparturient dairy cows. Animals 2015; 5: 793-802 DOI: 10.3390/ani5030384.
- 36 Grummer R.. Etiology of lipid-related metabolic disorders in periparturient dairy cows. J Dairy Sci 1993; 76: 3882-3896 DOI: 10.3168/jds.S0022-0302(93)77729-2.
- 37 Pullen D, Liesman J, Emery R.. A species comparison of liver slice synthesis and secretion of triacylglycerol from nonesterified fatty acids in media. J Anim. Sci 1990; 68: 1395-1399 DOI: 10.2527/1990.6851395x.
- 38 Adiels M, Westerbacka J, Soro-Paavonen A. et al. Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance. Diabetologia 2007; 50: 2356-2365 DOI: 10.1007/s00125-007-0790-1.
- 39 Glatz J, Luiken J.. Dynamic role of the transmembrane glycoprotein CD36 (SR-B2) in cellular fatty acid uptake and utilization. J Lipid Res 2018; 59: 1084-1093 DOI: 10.1194/jlr.R082933.
- 40 Barclay J, Nelson C, Ishikawa M. et al. GH-dependent STAT5 signalling plays an important role in hepatic lipid metabolism. Endocrinology 2011; 152: 181-92 DOI: 10.1210/en.2010-0537.
- 41 Koonen P, Febbraio M, Bonnet S. et al. CD36 expression contributes to dyslipidemia with diet-induced obesity. Circulation 2007; 116: 2139-2147 DOI: 10.1161/CIRCULATIONAHA.107.712901.
- 42 Wilson C, Tran J, Erion D. et al. Hepatocyte-specific disruption of CD36 attenuates fatty liver and improves insulin sensitivity in HFD-fed mice. Endocrinology 2016; 157: 570-85 DOI: 10.1210/en.2015-1866..
- 43 McCarthy S, Waters S, Kenny D. et al. Negative energy balance and hepatic gene expression patterns in high-yielding dairy cows during the early postpartum period: A global approach. Physiological Genomics 2010; 42A: 188-199 DOI: 10.1152/physiolgenomics.00118.2010.
- 44 Wathes D, Cheng C, Salavati M. et al. Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation. J Dairy Sci 2021; 104: 3596-3616 DOI: 10.3168/jds.2020-19165.
- 45 Butler S, Marr A, Pelton S. et al. Insulin restores GH responsiveness during lactation-induced negative energy balance in dairy cattle: effects on expression of IGF-I and GH receptor 1A. J. Endocrinology 2003; 176: 205-217 DOI: 10.1677/joe.0.1760205.
- 46 Rhoads R, Kim J, Leury B. et al. Insulin increases the abundance of the growth hormone receptor in liver and adipose tissue of periparturient cows. J Nutr 2004; 134: 1920-1927 DOI: 10.1093/jn/134.5.1020.
- 47 Mashek D, Ingvartsen K, Andersen J. et al. Effects of a four-day hyper-insulinemic-euglycemic clamp in early and mid-lactation dairy cows on plasma concentrations of metabolites, hormones, and binding proteins. Domestic Animal Endocrinol 2001; 21: 169-85 DOI: 10.1016/S0739-7240(01)00112-6.
- 48 Lucy M, Escalante R, Keisler D. et al. Short communication: Glucose infusion into early postpartum cows defines an upper physiological set point for blood glucose and causes rapid and reversible changes in blood hormones and metabolites. J Dairy Sci 2013; 96: 5762-5768 DOI: 10.3168/jds.2013-6794.
- 49 Carra M, Al-Trad B, Penner G. et al. Intravenous infusions of glucose stimulate key lipogenic enzymes in adipose tissue of dairy cows in a dose-dependent manner. J Dairy Sci 2013; 96: 4299-4309 DOI: 10.3168/jds.2012-6242.
- 50 McCarthy C., Dooley B, Branstad E. et al. Energetic metabolism, milk production, and inflammatory response of transition dairy cows fed rumen-protected glucose. J Dairy Sci 2020; 103: 7431-7461 DOI: 10.3168/jds.2020-18151.
- 51 Gross J, Schwarz F, Eder K. et al. Liver fat content and lipid metabolism in dairy cows during early lactation and during a mid-lactation feed restriction. J Dairy Sci 2013; 96: 5008-5017 DOI: 10.3168/jds.2012-6245.
- 52 Loor J, Everts R, Bionaz M. et al. Nutrition-induced ketosis alters metabolic and signalling gene networks in liver of periparturient dairy cows. Physiol. Genomics 2007; 32: 105-16 DOI: 10.1152/physiolgenomics.00188.2007.
- 53 Hayirli A, Bertics S, Grummer R.. Effects of slow-release insulin on production, liver triglyceride, and metabolic profiles of Holsteins in early lactation. J Dairy Sci 2002; 85: 2180-2191 DOI: 10.3168/jds.S0022-0302(02)74297-5.
- 54 Smith K, Butler W, Overton T.. Effects of prepartum 2,4-thiazolidinedione on metabolism and performance in transition dairy cows. J Dairy Sci 2009; 92: 3623-3633 DOI: 10.3168/jds.2008-1508.
- 55 Fürll M.. (persönliche Mitteilung; unveröffentlicht)
- 56 Nafikov R, Ametaj B, Bobe G. et al. Prevention of fatty liver in transition dairy cows by subcutaneous injections of glucagon. J Dairy Sci 2006; 89: 1533-1545 DOI: 10.3168/jds.S0022-0302(06)72221-4.
- 57 Harrison R, Ford S, Young J. et al. Increased milk production versus reproductive and energy status of high producing cows. J Dairy Sci 1990; 73: 2749-2758 DOI: 10.3168/jds.S0022-0302(90)78960-6.
- 58 Giesecke D.. Insulin deficiency and metabolic disorders in high-yielding dairy cows. J South Afr Vet Ass 1986; 57: 67-70
- 59 Humer E, Khol-Parisini A, Metzler-Zebeli B. et al. Alterations of the lipid metabolome in dairy cows experiencing excessive lipolysis early postpartum. PLoS One 2016; 11: e0158633 DOI: 10.1371/ journal.pone.0158633.
- 60 Zinicola M, Bicalho R.. Association of peripartum plasma insulin concentration with milk production, colostrum insulin levels, and plasma metabolites of Holstein cows. J Dairy Sci 2019; 102: 1473-1482 DOI: 10.3168/jds.2017-14029.
- 61 McGlymont G, Vallance S.. Depression of blood glycerides and milk fat synthesis by glucose infusion. Proc. Nutr. Soc. 1962; 21: xli-xlii
- 62 Martens H.. Transition period of the dairy cow revisited: II. Homeorhetic. stimulus and ketosis with implication for fertility. J Agric Sci 2020; 12: 25-54 DOI: 10.5539/jas.v12n3p25.
- 63 Sakai T, Hayakawa T, Hamakawa M. et al. Therapeutic effects of simultaneous use of glucose and insulin in ketotic cows. J Dairy Sci 1993; 76: 109-114 DOI: 10.3168/jds.S0022-0302(93)77329-4.
- 64 Ingvartsen K, Friggens N.. To what extend do variabilities in hormones, metabolites and energy intake explain variability in milk yield? Domest. Animal Endocrinol 2005; 29: 294-304 DOI: 10.1016/j.domaniend.2005.05.001.
- 65 Gulay M, Hayen M, Liboni M. et al. Low doses of bovine somatotropin during the transition period and early lactation improves milk yield, efficiency of production, and other physiological responses of Holstein cows. J Dairy Sci 2004; 97: 946-960 DOI: 10.3168/jds.S0022-0302(04)73239-7.
- 66 Silva P, Soares H, Braz W. et al. Effects of treatment of periparturient dairy cows with recombinant bovine somatotropin on health and productive and reproductive parameters. J Dairy Sci 2017; 100: 3126-3142 DOI: 10.3168/jds.2016-11737.
- 67 Gohary K, Leslie K, Ford J. et al. Effect of administration of recombinant bovine somatotropin on health and performance of lactating dairy cows diagnosed with hyperketonemia. J Dairy Sci 2016; 99: 4392-4400 DOI: 10.3168/jds.2014-8235.
- 68 Bremmer D, Bertics S, Besong S. et al. Changes in hepatic microsomal triglyceride transfer protein and triglyceride in periparturient dairy cattle. J Dairy Sci 2000; 83: 2252-2260 DOI: 10.3168/jds.S0022-0302(00)75109-5.
- 69 Schlegel G, Ringseis R, Keller J. et al. Expression of fibroblast growth factor 21 in the liver of dairy cows in the transition period and during lactation. Journal of Animal Physiol. Animal Nutr 2013; 97: 820-829 DOI: 10.1111/j.1439-0396.2012.01323.x.
- 70 Fisher M, Maratos-Flier E.. Understanding the physiology of FGF21. Annual Review Physiol 2016; 78: 223-241 DOI: 10.1146/annurev-physiol-021115-105339.
- 71 Laeger T, Henagan T, Albarado D. et al. FGF21 is an endocrine signal of protein restriction. J Clin. Invest 2014; 124: 3913-3922 DOI: 10.1172/JCI74915.
- 72 Schoenberg K, Giesy S, Harvatine K. et al. Plasma FGF21 is elevated by the intense lipid mobilization of lactation. Endocrinology 2011; 152: 4652-4661 DOI: 10.1210/en.2011-1425.
- 73 Hotta Y, Nakamura H, Konishi M. et al. Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver. Endocrinology 2009; 150: 4625-463 DOI: 10.1210/en.2009-0119.
- 74 Xu J, Lloyd D, Hale C. et al. Fibroblast growth factor 21 reverse hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 2009; 58: 250-259 DOI: 10.2337/db08-0392.
- 75 Caixeta L, Giesy S, Krumm C. et al. Effect of circulating glucagon and free fatty acids on hepatic FGF21 production in dairy cows. Am J Physiol Regul Integr Comp Physiol 2017; 313: R526-R534 DOI: 10.1152/ajpregu.00197.2017.
- 76 Krumm C, Giesy S, Caixeta L. et al. Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. I. Effects of signaling and indices of insulin action. J Dairy Sci 2019; 102: 11597-11608 DOI: 10.3168/jds.2019-16696.
- 77 Caixeta L, Giesy S, Krumm C. et al. Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. II. Pharmacokinetics, whole-animal performance, and lipid metabolism. J Dairy Sci 2019; 102: 11597-11608 DOI: 10.3168/jds.2019-16696.
- 78 Eder K, Denise K, Gessner D, Ringseis R.. Fibroblast growth factor 21 in dairy cows: Current knowledge and potential relevance. J Animal Sci. Biotech 2021; 12: 97 DOI: 10.1186/s40104-021-00621-y.
- 79 Lamb C, Giesy S, McGuckin M. et al. Fibroblast growth factor-21 improves insulin action in nonlactating ewes. Am. J.Physiol. Regul. Integr. Comp. Physiol. 2022; 322: R170-R180 DOI: 10.1152/ajpregu.00259.2021.
- 80 Khan M, Jacometo C, Graugnard D. et al. Overfeeding dairy cattle during late-pregnancy alters hepatic PPARα-regulated pathways including hepatokines: Impact on metabolism and peripheral insulin sensitivity. Gen. Regul. Syst. Biol 2014; 8: 97-111 DOI: 10.4137/GRSB.S14116.
- 81 Carriquiry M, Weber W, Fahrenkrug S. et al. Hepatic gene expression in multiparous Holstein cows treated with bovine somatotropin and fed n-3 fatty acids in early lactation. J Dairy Sci 2009; 92: 4889-4900 DOI: 10.3168/jds.2008-1676.
- 82 Boisclair Y.. (Persönliche Mitteilung 2022)
- 83 Scharrer E.. Control of food intake by fat acid oxidation and ketogenesis. Nutrition 1999; 15: 704-714 DOI: 10.1016/S0899-9007(99)00125-2.
- 84 Lean I, Farver T, Troutt H. et al. Time series cross-correlation analysis of postparturient relationships among serum metabolites and yield variables in Holstein cows. J Dairy Sci 1992; 75: 1891-900 DOI: 10.3168/jds.S0022-0302(92)77949-1.
- 85 Xu Ch, Liu G, Li X. et al. decreased complete oxidation capacity of fatty acids in the liver of ketotic cows. Asian-Australian J Anim Sci 2010; 23: 312-317 DOI: 10.5713/ajas.2010.90416.
- 86 Murondoti A, Jorritsma R, Beynen A. et al. Activities of the enzymes of hepatic gluconeogenesis in periparturient cows with induced fat liver. J Dairy Res 2004; 71: 129-134 DOI: 10.1017/S0022029904000020.
- 87 Du X, Zhu Y, Peng Z. et al. High concentrations of fat acids and β-hydroxybutyrate impair the growth hormone-mediated hepatic JAK2-STAT5 pathway in clinically ketotic cows. J Dairy Sci 2018; 101: 3476-3487 DOI: 10.3168/jds.2017-13234.
- 88 Demigné C, Yacoub C, Rémésy C. et al. Propionate and butyrate metabolism in rat or sheep hepatocytes. Biochim. Biophys. Acta 1986; 875: 535-842 DOI: 10.1016/0005-2760(86)90074-3.
- 89 Schlumbohm C, Harmeyer J.. Hyperketonemia impairs glucose metabolism in pregnant and nonpregnant ewes. J Dairy Sci 2004; 87: 350-358 DOI: 10.3168/jds.S0022-0302(04)73174-4.
- 90 Zarrin M, De Matteis L, Vernay M. et al. Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolism. J Dairy Sci 2013; 96: 2960-2972 DOI: 10.3168/jds.2012-6224.
- 91 Sordillo L, Mavangira V.. The nexus between nutrient metabolism, oxidative stress and inflammation in transition cows. Animal Production Science 2014; 54: 1204-1214 DOI: 10.1071/AN14503.
- 92 Sordillo L, Raphael W.. Significance of metabolic stress, lipid mobilization, and inflammation on transition cow disorders. Vet. Clin. Food Anim 2013; 29: 267-278 DOI: 10.1016/j.cvfa.2013.03.002.
- 93 Abuelo J, Gandy L, Neuder J, Brester L, Sordillo M.. Short communication: Markers of oxidant status and inflammation relative to the development of claw lesions associated with lameness in early lactation cows. J Dairy Sci 2016; 99: 5640-5648 DOI: 10.3168/jds.2015-10707.
- 94 Ametaj B, Bradford B, Bode G. et al. Strong relationships between mediators of the acute phase response and fatty liver in dairy cows. Can J Anim Sci 2005; 85: 165-175 DOI: 10.4141/A04-043.
- 95 Abuajamich M, Kvidera S, Sanz Fernandez M. et al. Inflammatory biomarkers are associated with ketosis in periparturient Holstein cows. Res. Vet. Sci. 2016; 109: 81-85 DOI: 10.1016/j.rvsc.2016.09.015.
- 96 Ohtsuka H, Koiwa M, Hatsugaya A. et al. Relationship between serum TNF activity and insulin resistance in dairy cows affected with naturally occurring fat liver. J Vet. Med. Sci 2001; 63: 1021-1025 DOI: 10.1292/jvms.63.1021.
- 97 Bradford B, Mamedova L, Minton J. et al. Daily injection of tumor necrosis factor-α increases hepatic triglycerides and alters transcript abundances of metabolic genes in lactation dairy cattle. J Nutr 2009; 139: 1451-1456 DOI: 10.3945/ jn.109.108233.
- 98 Contreras G, Strieder-Barboza C, Raphael W.. Adipose tissue lipolysis and remodelling during transition period of dairy cows. J Anim Sci Biotech 2017; 8: 41 DOI: 10.1186/s40104-017-0174-4.
- 99 Horst E, Kvidera S, Baumgard L.. Invited review: The influence of immune activation on transition cow health and performance – A critical evaluation of traditional dogmas. J Dairy Sci 2021; 104: 8380-8410 DOI: 10.3168/jds.2021-20330.
- 100 Zachut M, Contreras A.. Symposium review: Mechanistic insights into adipose tissue inflammation and oxidative stress in perparturient dairy cows. J Dairy Sci 2022; 105: 3670-3686 DOI: 10.3168/jds.2021-21225.
- 101 Ametaj B.. A new understanding of the causes of fatty liver in dairy cows. Adv. Dairy Technol 2005; 17: 97-112
- 102 Horst E, Kvidera S, Dickson M. et al. Effects of continuous and increasing lipopolysaccharide infusion on basal and stimulated metabolism in lactating Holstein cows. J Dairy Sci 2019; 102: 3584-3597 DOI: 10.3168/jds.2018-15627.
- 103 Horst E, van den Brink M, Mayorga E. et al. Evaluating acute inflammation’s effects on hepatic triglyceride content in experimentally induced hyperlipidemic dairy cows in late lactation. J Dairy Sci 2020; 103: 9620-9633 DOI: 10.3168/jds.2020-18686.
- 104 Xu C, Liu G., Li X. et al. Decreased complete oxidation capacity of fatty acids in the liver of ketotic cows. Asian-Austr. J Anim Sci 2010; 23: 312-317
- 105 Song Y, Li X, Li Y. et al. Non-esterified fatty acids activate the ROS–p38 p53/Nrf2 signalling pathway to induce bovine hepatocyte apoptosis in vitro. Apoptosis 2014; 19: 984-997 DOI: 10.1007/s10495-014-0982-3.
- 106 Gessner D, Ringseis R, Eder K.. Potential of plant polyphenols to combat oxidative stress and inflammatory processes in farm animals. J Anim Physiol Anim Nutr 2017; 101: 605-628 DOI: 10.1111/jpn.12579.
- 107 Han J, Kaufmann R.. The role of ER stress in lipid metabolism and lipotoxicity. J Lip Res 2016; 57: 1329-1338 DOI: 10.1194/jlr.R067595.
- 108 Ringseis R, Gessner D, Eder K.. Molecular insights into the mechanisms of liver-associated diseases in early-lactating dairy cows: hypothetical role of endoplasmic reticulum stress. J Anim Physiol Anim Nutr 2015; 99 DOI: 10.1111/jpn.12263.
- 109 Xu Q, Fan Y, Loor J. et al. Effects of diacylglycerol O-acyltransferase 1 (DGAT1) on endoplasmic reticulum stress and inflammatory responses in adipose tissue of ketotic dairy cows. J Dairy Sci 2022; 105: 9191-926 DOI: 10.3168/jds.2022-21989.
- 110 Bauman D, Currie E.. Partitioning of nutrients during pregnancy and lactation. J Dairy Sci 1980; 63: 1514-1529 DOI: 10.3168/jds.s0022-0302(80)83111-0.
- 111 Radcliff P, McCormick B, Keisler D. et al. Partial feed restriction decreases growth hormone receptor 1A mRNA expression in postpartum dairy cows. J Dairy Sci 2006; 89: 611-619 DOI: 10.3168/jds.S0022-0302(06)72124-5.
- 112 Snedec T, Bittner-Schwerda L, Rachidi F. et al. Effects of an intensive experimental protocol on health, fertility, and production in transition dairy cows. J Dairy Sci 2021; 104: 5310-5326 DOI: 10.3168/jds.2021-20673113..
- 113 Herdt Th, Goeders L, Liesman J. et al. Test for estimation of bovine hepatic lipid content. J Am Vet Med Ass 1983; 182: 953-955.114
- 114 Starke A, Haudum A, Weijers G. et al. Noninvasive detection of hepatic lipidosis in dairy cows with calibrated ultrasonographic image analysis. J Dairy Sci. 2010; 93: 2952-2965 DOI: 10.3168/ds.2009-2584.
- 115 Gong Z, Tas E, Yakar S. et al. Hepatic lipid metabolism and non-alcoholic fatty liver disease in aging. Mol. Cell. Endocrinology 2017; 455: 115-130 DOI: 10.1016/j.mce.2016.12.022.
- 116 Rada P, González-Rodríguez Á, García-Monzón C. et al. Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?. Cell Death Dis 2020; 11: 802 DOI: 10.1038/s41419-020-03003-w.
- 117 Nishizawa H, Iguchi G, Murawaki A. et al. Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy. Eur. J Endocrinol 2020; 167: 67-74 DOI: 10.1530/EJE-12-0252.
- 118 Liu Z, Cordoba-Chacon J, Kineman R. et al. Growth Hormone Control of Hepatic Lipid Metabolism. Diabetes 2016; 65: 3598-3609 DOI: 10.2337/db16-0649119.
- 119 Zachut M, Honig H, Striem S. et al. Periparturient dairy cows do not exhibit hepatic insulin resistance, yet adipose-specific insulin resistance occurs in cows prone to high weight loos. J Dairy Sci. 2013; 96: 5656-5669 DOI: 10.3168/jds.2012-6142.
- 120 Fenwick M, Fitzpatrick R, Kenny D. et al. Interrelationships between negative energy balance (NEB) and IGF regulation in liver of lactating cows. Dom. Anim. Endocrinology 2008; 34: 31-44 DOI: 10.1016/j.domaniend.2006.10.002.
- 121 McGuire M, Bauman D, Wendie D. et al. Nutritional modulation of the somatotropin/insulin-like-factor system: Response to feed deprivation in lactating cows. J Nutr 1995; 125: 493-502 DOI: 10.1093/jn/125.3.493.
- 122 McArt J, Nydam D, Oetzel G. et al. Elevated non-esterified fat acids and β-hydroxybutyrate and their association with transition dairy cows performance. Vet J 2013; 198: 560-570 DOI: 10.1016/j.tvjl.2013.08.011.
- 123 Schären M, Snedec T, Riefke B. et al. Aspects of transition cow metabolomics-Part I: Effects of a metaphylactic butaphosphan and cyanocobalamin treatment on the metabolome in liver, blood, and urine in cows with different liver metabotypes. J Dairy Sci 2021; 104: 9205-9226 DOI: 10.3168/jds.2020-19055.
- 124 Zhu L, Armentano L, Bremmer D. et al. Plasma concentrations of urea, ammonia, glutamine around calving and the relation to hepatic triglyceride, to plasma ammonia removal and blood acid-base balance. J Dairy Sci. 2000; 83: 734-740 DOI: 10.3168/jds.S0022-0302(00)74935-6.
- 125 Strang B, Bertics S, Grummer R. et al. Effect of long-chain fatty acids on triglyceride accumulation, gluconeogenesis, and ureagenesis in bovine hepatocytes. J Dairy Sci 1998; 81: 728-739 DOI: 10.3168/jds.S0022-0302(98)75629-2.
- 126 Strang B, Bertics S, Grummer R. et al. Relationship of trigyceride accumulation to insulin clearance and hormonal responsiveness in bovine hepatocytes. J Dairy Sci 1998; 81: 740-747 DOI: 10.3168/jds.S0022-0302(98)75630-9.
- 127 Schären M, Riefke B, Slopianka M. et al. Aspects of transition cow metabolomics-Part III: Alterations in the metabolome of liver and blood throughout the transition period in cows with different liver metabotypes. J Dairy Sci. 2021; 104: 9245-9262 DOI: 10.3168/jds.2020-19056.
- 128 Song Y, Loor J, Li C. et al. Enhanced mitochondrial dysfunction and oxidative stress in the mammary gland of cows with clinical ketosis. J Dairy Sci 2021; 104: 6009-6918 DOI: 10.3168/jds.2020-19964.
- 129 Bremmer D, Trower S, Bertics S. et al. Etiology of fatty liver in Dairy cattle: Effects of nutrition and hormonal status on hepatic microsomal triglyceride transfer protein. J Dairy Sci 2000; 83: 2239-2251 DOI: 10.3168/jds.S0022-0302(00)75108-3.
- 130 Wu Z, Yu Y, Alugongo G. et al. Short communication: Effects of an immunomodulatory feed additive on phagocytic capacity of neutrophils and relative gene expression in circulating white blood cells of transition Holstein cows. J Dairy Sci 2017; 100: 7549-7555 DOI: 10.3168/jds. 2016-12528.
- 131 Raboisson D, Mounié M, Maigné E.. Diseases, reproductive performance, and changes in milk production associated with subclinical ketosis in dairy cows: A meta-analysis and review. J Dairy Sci 2014; 97: 7547-7563 DOI: 10.3168/jds.2014-8237.
- 132 Koeck A, Miglior F, Jamrozik J. et al. Genetic association of ketosis with milk production traits in early lactation of Canadian Holstein. J Dairy Sci 2013; 96: 4688-4696 DOI: 10.3168/jds.2012-6408.