Dataset Information

Hepatic pyruvate carboxylase expression differed prior to hyperketonemia onset in transition dairy cows.

ABSTRACT: Fatty acids (FA) provide an energy source to the liver during negative energy balance; however, when FA influx is excessive, FA can be stored as liver lipids or incompletely oxidized to ?-hydroxybutyrate (BHB). The objectives of this study were to quantify plasma and liver FA profiles and hepatic gene expression in cows diagnosed with hyperketonemia (HYK; BHB ? 1.2 mM) or not (nonHYK; BHB < 1.2 mM) to determine a relationship between FA profile and expression of hepatic genes related to oxidation and gluconeogenesis. Production parameters, blood samples (-28, -3, 1, 3, 5, 7, 9, 11, and 14 d relative to parturition; n = 28 cows), and liver biopsies (1, 14, and 28 d postpartum; n = 22 cows) were collected from Holstein cows. Cows were retrospectively grouped as HYK or nonHYK based on BHB concentrations in postpartum blood samples. Average first positive test (BHB ? 1.2 mM) was 9 ± 5 d (± SD). Cows diagnosed with HYK had greater C18:1 and lower C18:2 plasma proportions. Liver FA proportions of C16:0 and C18:1 were related to proportions in plasma, but C18:0 and C18:2 were not. Some interactions between plasma FA and HYK on liver FA proportion suggests that there may be preferential use depending upon metabolic state. Cows diagnosed with HYK had decreased pyruvate carboxylase (PC) expression, but no difference at 1 d postpartum in either cytosolic or mitochondrial isoforms of phosphoenolpyruvate carboxykinase (PCK). The increased PC to PCK ratios in nonHYK cows suggests the potential for greater hepatic oxidative capacity, coinciding with decreased circulating BHB. Interestingly, FA, known regulators of PC expression, were not correlated with PC expression at 1 d postpartum. Taken together, these data demonstrate that HYK cows experience a decrease in the ratio of hepatic PC to PCK at 1 day postpartum prior to HYK diagnosis which, on average, manifested a week later. The differential regulation of PC involved in HYK diagnosis may not be completely due to shifts in FA profiles and warrants further investigation.

SUBMITTER: Weld KA

PROVIDER: S-EPMC7652276 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hepatic pyruvate carboxylase expression differed prior to hyperketonemia onset in transition dairy cows.

Weld Kristina A KA Caputo Oliveira Rafael R Bertics Sandra J SJ Erb Sophia J SJ White Heather M HM

PloS one 20201109 11

Fatty acids (FA) provide an energy source to the liver during negative energy balance; however, when FA influx is excessive, FA can be stored as liver lipids or incompletely oxidized to β-hydroxybutyrate (BHB). The objectives of this study were to quantify plasma and liver FA profiles and hepatic gene expression in cows diagnosed with hyperketonemia (HYK; BHB ≥ 1.2 mM) or not (nonHYK; BHB < 1.2 mM) to determine a relationship between FA profile and expression of hepatic genes related to oxidatio ...[more]

PMID: 33166331

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Project description:Metabolic maladaptation in dairy cows after calving can lead to long-term elevation of ketones, such as β-hydroxybutyrate (BHB), representing the condition known as hyperketonemia, which greatly influences the health and production performance of cows during the lactation period. Although the gut microbiota is known to alter in dairy cows with hyperketonemia, the association of microbial metabolites with development of hyperketonemia remains unknown. In this study, we performed a multi-omics analysis to investigate the associations between fecal microbial community, fecal/plasma metabolites, and serum markers in hyperketonemic dairy cows during the transition period. Dynamic changes in the abundance of the phyla Verrucomicrobiota and Proteobacteria were detected in the gut microbiota of dairy cows, representing an adaptation to enhanced lipolysis and abnormal glucose metabolism after calving. Random forest and univariate analyses indicated that Frisingicoccus is a key bacterial genus in the gut of cows during the development of hyperketonemia, and its abundance was positively correlated with circulating branched-chain amino acid levels and the ketogenesis pathway. Taurodeoxycholic acid, belonging to the microbial metabolite, was strongly correlated with an increase in blood BHB level, and the levels of other secondary bile acid in the feces and plasma were altered in dairy cows prior to the diagnosis of hyperketonemia, which link the gut microbiota and hyperketonemia. Our results suggest that alterations in the gut microbiota and its metabolites contribute to excessive lipolysis and insulin insensitivity during the development of hyperketonemia, providing fundamental knowledge about manipulation of gut microbiome to improve metabolic adaptability in transition dairy cows.IMPORTANCEAccumulating evidence is pointing to an important association between gut microbiota-derived metabolites and metabolic disorders in humans and animals; however, this association in dairy cows from late gestation to early lactation is poorly understood. To address this gap, we integrated longitudinal gut microbial (feces) and metabolic (feces and plasma) profiles to characterize the phenotypic differences between healthy and hyperketonemic dairy cows from late gestation to early lactation. Our results demonstrate that cows underwent excessive lipid mobilization and insulin insensitivity before hyperketonemia was evident. The bile acids are functional readouts that link gut microbiota and host phenotypes in the development of hyperketonemia. Thus, this work provides new insight into the mechanisms involved in metabolic adaptation during the transition period to adjust to the high energy and metabolic demands after calving and during lactation, which can offer new strategies for livestock management involving intervention of the gut microbiome to facilitate metabolic adaptation.

Project description:BackgroundForage plays critical roles in milk performance of dairy. However, domestic high-quality forage such as alfalfa hay is far from being sufficient in China. Thus, more than 1 million tons of alfalfa hay were imported in China annually in recent years. At the same time, more than 10 million tons of corn stover are generated annually in China. Thus, taking full advantage of corn stover to meet the demand of forage and reduce dependence on imported alfalfa hay has been a strategic policy for the Chinese dairy industry. Changes in liver metabolism under different forage resources are not well known. Thus, the objective of the present study was to investigate the effect of different forage resources on liver metabolism using RNAseq and bioinformatics analyses.ResultsThe results of this study showed that the cows fed a diet with corn stover (CS) as the main forage had lower milk yield, DMI, milk protein content and yield, milk fat yield, and lactose yield than cows fed a mixed forage (MF) diet (P < 0.01). KEGG analysis for differently expressed genes (DEG) in liver (81 up-regulated and 423 down-DEG, Padj ≤0.05) showed that pathways associated with glycan biosynthesis and metabolism and amino acid metabolism was inhibited by the CS diet. In addition, results from DAVID and ClueGO indicated that biological processes related to cell-cell adhesion, multicellular organism growth, and amino acid and protein metabolism also were downregulated by feeding CS. Co-expression network analysis indicated that FAM210A, SLC26A6, FBXW5, EIF6, ZSCAN10, FPGS, and ARMCX2 played critical roles in the network. Bioinformatics analysis showed that genes within the co-expression network were enriched to "pyruvate metabolic process", "complement activation, classical pathway", and "retrograde transport, endosome to Golgi".ConclusionsResults of the present study indicated that feeding a low-quality forage diet inhibits important biological functions of the liver at least in part due to a reduction in DMI. In addition, the results of the present study provide an insight into the metabolic response in the liver to different-quality forage resources. As such, the data can help develop favorable strategies to improve the utilization of corn stover in China.

Project description:In the heart, detection of hyperpolarized [(13)C]bicarbonate and (13)CO(2) by magnetic resonance (MR) after administration of hyperpolarized [1-(13)C]pyruvate is caused exclusively by oxidative decarboxylation of pyruvate via the pyruvate dehydrogenase complex (PDH). However, liver mitochondria possess alternative anabolic pathways accessible by [1-(13)C]pyruvate, which may allow a wider diagnostic range for hyperpolarized MR compared with other tissue. Metabolism of hyperpolarized [1-(13)C]pyruvate in the tricarboxylic acid (TCA) cycle was monitored in the isolated perfused liver from fed and fasted mice. Hyperpolarized [1-(13)C]pyruvate was rapidly converted to [1-(13)C]lactate, [1-(13)C]alanine, [1-(13)C]malate, [4-(13)C]malate, [1-(13)C]aspartate, [4-(13)C]aspartate, and [(13)C]bicarbonate. Livers from fasted animals had increased lactate:alanine, consistent with elevated NADH:NAD(+). The appearance of asymmetrically enriched malate and aspartate indicated high rates of anaplerotic pyruvate carboxylase activity and incomplete equilibration with fumarate. Hyperpolarized [(13)C]bicarbonate was also detected, consistent with multiple mechanisms, including cataplerotic decarboxylation of [4-(13)C]oxaloacetate via phosphoenolpyruvate carboxykinase (PEPCK), forward TCA cycle flux of [4-(13)C]oxaloacetate to generate (13)CO(2) at isocitrate dehydrogenase, or decarboxylation of [1-(13)C]pyruvate by PDH. Isotopomer analysis of liver glutamate confirmed that anaplerosis was sevenfold greater than flux through PDH. In addition, signal from [4-(13)C]malate and [4-(13)C]aspartate was markedly blunted and signal from [(13)C]bicarbonate was completely abolished in livers from PEPCK KO mice, indicating that the major pathway for entry of hyperpolarized [1-(13)C]pyruvate into the hepatic TCA cycle is via pyruvate carboxylase, and that cataplerotic flux through PEPCK is the primary source of [(13)C]bicarbonate. We conclude that MR detection of hyperpolarized TCA intermediates and bicarbonate is diagnostic of pyruvate carboxylase and PEPCK flux in the liver.

Dataset Information

Hepatic pyruvate carboxylase expression differed prior to hyperketonemia onset in transition dairy cows.

Publications

Hepatic pyruvate carboxylase expression differed prior to hyperketonemia onset in transition dairy cows.

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