Expression of genes involved in hepatic carnitine synthesis and uptake in dairy cows in the transition period and at different stages of lactation

Abstract

BackgroundIn rodents and pigs, it has shown that carnitine synthesis and uptake of carnitine into cells are regulated by peroxisome proliferator-activated receptor α (PPARA), a transcription factor which is physiologically activated during fasting or energy deprivation. Dairy cows are typically in a negative energy balance during early lactation. We investigated the hypothesis that genes of carnitine synthesis and uptake in dairy cows are enhanced during early lactation.ResultsmRNA abundances of PPARA and some of its classical target genes and genes involved in carnitine biosynthesis [trimethyllysine dioxygenase (TMLHE), 4-N-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1), γ-butyrobetaine dioxygenase (BBOX1)] and uptake of carnitine [novel organic cation transporter 2 (SLC22A5)] as well as carnitine concentrations in liver biopsy samples of 20 dairy cows in late pregnancy (3 wk prepartum) and early lactation (1 wk, 5 wk, 14 wk postpartum) were determined. From 3 wk prepartum to 1 wk postpartum, mRNA abundances of PPARΑ and several PPARΑ target genes involved in fatty acid uptake, fatty acid oxidation and ketogenesis in the liver were strongly increased. Simultaneously, mRNA abundances of enzymes of carnitine synthesis (TMLHE: 10-fold; ALDH9A1: 6-fold; BBOX1: 1.8-fold) and carnitine uptake (SLC22A5: 13-fold) and the concentration of carnitine in the liver were increased from 3 wk prepartum to 1 wk postpartum (P < 0.05). From 1 wk to 5 and 14 wk postpartum, mRNA abundances of these genes and hepatic carnitine concentrations were declining (P < 0.05). There were moreover positive correlations between plasma concentrations of non-esterified fatty acids (NEFA) and hepatic carnitine concentrations at 1 wk, 5 wk and 14 wk postpartum (P < 0.05).ConclusionsThe results of this study show for the first time that the expression of hepatic genes of carnitine synthesis and cellular uptake of carnitine is enhanced in dairy cows during early lactation. These changes might provide an explanation for increased hepatic carnitine concentrations observed in 1 wk postpartum and might be regarded as a physiologic means to provide liver cells with sufficient carnitine required for transport of excessive amounts of NEFA during a negative energy balance.

Liver fat content and lipid metabolism in dairy cows during early lactation and during a mid-lactation feed restriction

“…Mean expression of SLC27A1 was highest in wk 1 p.p. in the present study along with highest plasma NEFA and liver TG concentration, in agreement with Schlegel et al (2012), and interestingly elevated for feed-restricted cows compared with control cows. To our knowledge, this paper shows distinct results on expression of SLC27A1 in the bovine liver during feed restriction in mid lactation for the first time.…”

“…An aliquot (~40 mg) of the liver tissue was frozen immediately at −20°C until determination of TG content. Liver TG content was measured after extraction according to Schlegel et al (2012). In brief, lipids from biopsy tissue were extracted with a mixture of n-hexane and isopropanol (3:2, vol/vol).…”

Tissues, Metabolic Pathways and Genes of Key Importance in Lactating Dairy Cattle

“…The key genes that are involved in regulating energy metabolism in multiple tissues include PPRA, PCK1, PCK, ACACA, FASN, FBP2, FABP3, PPARGC1A, ACSL1, PPARGC1A, AGPAT6, PCCA, LPIN1, ACO, CPT-I, CPT-II and ACSL [4,15,27,94,131,163]. These genes are involved in fatty acid uptake (mainly in the liver and mammary gland), mitochondrial and peroxisomal fatty acid oxidation, ketone body metabolism (ketogenesis) and cholesterol metabolism (in liver) early in lactation in dairy cattle [135] and are discussed in the following tissue-specific sections in more detail.…”

“…1), and TAG in liver [129,135]. Several genes and pathways in multiple tissues are involved in regulating these metabolites in lactating dairy cows [14,15,23,53,90,98,135]. A gene-based mapping and pathway analysis indicated that three pathways (steroid hormone biosynthesis, ether lipid metabolism and glycerophospholipid metabolism) jointly affect the concentrations of NEFA, BHBA and glucose in cows during the transition period [53].…”

“…The increase in lipid metabolism results in an increase in concentrations of key metabolites NEFA and BHBA in plasma (Fig. 1), and TAG in liver [129,135]. Several genes and pathways in multiple tissues are involved in regulating these metabolites in lactating dairy cows [14,15,23,53,90,98,135].…”