title: Variable liver fat concentration as a proxy for body fat mobilization postpartum has minor effects on insulin-induced changes in hepatic gene expression related to energy metabolism in dairy cows.
abstract: The liver plays a central role in adaptation for energy requirements around calving, and changes in the effects of insulin on hepatic energy metabolism contribute to metabolic adaptation in dairy cows. Hepatic insulin effects may depend on body fat mobilization. The objective of this study was to investigate the effects of insulin on the hepatic gene expression of enzymes involved in energy metabolism and factors related to nutrition partitioning in cows with high and low total liver fat concentration (LFC) after calving. Holstein cows were retrospectively grouped according to their LFC after calving as a proxy for body fat mobilization. Cows were classified as low (LLFC; LFC <24% fat/dry matter; n = 9) and high (HLFC; LFC >24.4% fat/dry matter; n = 10) fat-mobilizing after calving. Euglycemic-hyperinsulinemic clamps [6 mU/(kg × min) of insulin for 6 h] were performed in wk 5 antepartum (ap) and wk 3 postpartum (pp). Before and at the end of the euglycemic-hyperinsulinemic clamps, liver biopsies were taken to measure the mRNA abundance of enzymes involved in carbohydrate and lipid metabolism, expression related to the somatotropic axis, and adrenergic and glucocorticoid receptors. The mRNA abundance of pyruvate carboxylase, cytosolic phosphoenolpyruvate carboxykinase (PEPCK; PCK1), acyl-CoA-dehydrogenase very long chain (ACADVL), and hydroxyl-methyl-glutaryl-CoA-synthase 1 increased, but the mRNA abundance of solute carrier family 2 (SLC2A2 and SLC2A4), growth hormone receptor 1A (GHR1A), insulin-like growth factor 1 (IGF1), sterol regulatory element binding factor 1, adrenoceptor α 1A, and glucocorticoid receptor decreased from ap to pp. Insulin treatment was associated with decreased PCK1, mitochondrial PEPCK, glucose-6-phosphatase, propionyl-CoA-carboxylase α, carnitine-palmitoyl-transferase 1A, ACADVL, and insulin receptor mRNA, but increased IGF1 and SLC2A4 mRNA ap and pp and GHR1A mRNA pp. The mRNA abundance of SLC2A4 was greater, and the mRNA abundance of GHR1A and IGF1 tended to be lower in LLFC than in HLFC. Administration of insulin, albeit at a supraphysiological dose, was associated with inhibition of gene expression related to glucose production and β-oxidation, but we observed variable effects in the degree of insulin depression of individual genes. Insulin status is important for regulation of nutrient partitioning, but different LFC pp had very little influence on changes in hepatic gene expression following administration of insulin.
authors.affiliation: Institute of Nutritional Physiology ("Oskar Kellner"), Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institute of Nutritional Physiology ("Oskar Kellner"), Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany.
authors.forename: C T
authors.initials: CT
authors.lastname: Schäff
authors.affiliation: Institute of Nutritional Physiology ("Oskar Kellner"), Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Kautzsch
authors.affiliation: Institute of Nutritional Physiology ("Oskar Kellner"), Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Börner
authors.affiliation: Institute of Nutritional Physiology ("Oskar Kellner"), Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Erdmann
authors.affiliation: Veterinary Physiology, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.
authors.forename: R M
authors.initials: RM
authors.lastname: Bruckmaier
authors.affiliation: Institute of Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Röntgen
authors.affiliation: Institute of Nutritional Physiology ("Oskar Kellner"), Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kuhla
authors.affiliation: Institute of Nutritional Physiology ("Oskar Kellner"), Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf 18196, Germany. Electronic address: hammon@fbn-dummerstorf.de.
authors.forename: H M
authors.initials: HM
authors.lastname: Hammon
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D050260:Carbohydrate Metabolism / Q000235:genetics; D002417:Cattle; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000502:physiology; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007774:Lactation / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D049590:Postpartum Period / Q000502:physiology
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D013006:Growth Hormone
keywords: dairy cow; energy metabolism; hepatic gene expression; insulin; somatotropic axis