Acylcarnitine profiles in serum and muscle of dairy cows receiving conjugated linoleic acids or a control fat supplement during early lactation

Abstract

Acylcarnitines (ACC) are formed when fatty acid (FA)-coenzyme A enters the mitochondria for β-oxidation and the tricarboxylic acid cycle through the carnitine shuttle. Concentrations of ACC may vary depending on the metabolic conditions, but can accumulate when rates of β-oxidation exceed those of tricarboxylic acid. This study aimed to characterize muscle and blood serum acylcarnitine profiles, to determine the mRNA abundance of muscle carnitine acyltransferases, and to test whether dietary supplementation (from d 1 in milk) with conjugated linoleic acids (CLA; 100 g/d; each 12% of trans-10,cis-12 and cis-9,trans-11 CLA; n = 11) altered these compared with control fat-supplemented cows (CTR; n = 10). Blood samples and biopsies from the semitendinosus musclewere collected on d −21, 1, 21, and 70 relative to parturition. Serum and muscle ACC profiles were quantified using a targeted metabolomics approach. The CLA supplement did not affect the variables examined. The serum concentration of free carnitine decreased with the onset of lactation. The concentrations of acetylcarnitine, hydroxybutyrylcarnitine, and the sum of short-chain ACC in serum were greater from d −21 to 21 than thereafter. The serum concentrations of long-chain ACC tetradecenoylcarnitine (C14:1) and octadecenoylcarnitine (C18:1) concentrations were greater on d 1 and 21 compared with d −21. Muscle carnitine remained unchanged, whereas short-and medium-chain ACC, including propenoylcarnitine (C3:1), hydroxybutyrylcarnitine, hydroxyhexanoylcarnitine, hexenoylcarnitine (C6:1), and pimelylcarnitine were increased on d 21 compared with d −21 and decreased thereafter. In muscle, the concentrations of long-chain ACC (from C14 to C18) were elevated on d 1. The mRNA abundance of carnitine palmitoyltransferase 1, muscle isoform (CPT1B) increased 2.8-fold from d −21 to 1, followed by a decline to nearly prepartum values by d 70, whereas that of CPT2 did not change over time. The majority of serum and muscle short-and long-chain ACC were positively correlated with the FA concentrations in serum, whereas serum carnitine and C5 were negatively correlated with FA. Time-related changes in the serum and muscle ACC profiles were demonstrated that were not affected by the CLA supplement at the dosage used in the present study. The elevated concentrations of long-chain ACC species in muscle and of serum acetylcarnitine around parturition point to incomplete FA oxidation were likely due to insufficient metabolic adaptation in response to the load of FA around parturition.

Alterations of the acylcarnitine profiles in blood serum and in muscle from periparturient cows with normal or elevated body condition

“…Thus, an elevation of this ratio has been described in CPT1 deficiency (Fingerhut et al, 2001). The CPT1 ratio was reduced in early lactation in both serum and muscle (only in HBCS cows), reflecting the increased entrance of long-chain acyl-CoA into the mitochondria, which is in line with previous observations in dairy cows (Yang et al, 2019). Incomplete FA β-oxidation downstream of CPT1 is revealed by altered AcylCN levels (Koves et al, 2008), as acyl-CoA under mitochondrial FA overload can be converted into AcylCN for transport out of the mitochondria (Koves et al, 2008;Millington and Stevens, 2011;Violante et al, 2013).…”

“…In this study, most of the medium-and long-chain AcylCN concentrations in muscle were unchanged by over-conditioning around calving, except for C12-DC and C14: 2 -OH, which did increase in early lactation in the muscle of HBCS cows. Elevated concentrations of long-chain AcylCN species around parturition in the skeletal muscle of dairy cows were observed previously (Yang et al, 2019). The concentrations of C14: 2 -OH on d −49 and d 3 were higher in the muscle of HBCS than NBCS cows.…”

“…This is consistent with the increased need for free carnitine to transfer LCFA originating from the intense lipomobilization in adipose tissue into the mitochondrial matrix to generate metabolic energy in dairy cows (Humer et al, 2016). In dairy cows, the 4789 reduction in serum free-carnitine during early lactation is likely due to the intense uptake of free carnitine by skeletal muscle to maintain intracellular concentrations (Schooneman et al, 2014;Yang et al, 2019).…”

Review: Lipid biology in the periparturient dairy cow: contemporary perspectives

“…In dairy cattle transitioning from gestation to lactation, the capacity to completely oxidize FA to CO 2 is lowered, whereas incomplete oxidation to acid-soluble metabolites is elevated (Litherland et al, 2011). In the muscle of transition cow, long-chain acylcarnitines accumulate with short-and medium-chain acylcarnitines during the peripartum (Yang et al, 2019), suggesting that β-oxidation to acetyl-CoA increased but the tricarboxylic acid cycle was downregulated. In sick transition cows (i.e.…”

Metabolome profiling in skeletal muscle to characterize metabolic alterations in over-conditioned cows during the periparturient period

“…Identification of specific metabolomic "signatures" associated with over-conditioning is of utmost importance to help to fill gaps in knowledge related to how metabolic homeostasis might be perturbed during the periparturient period. Our previous study in dairy cows in the medium BCS range suggests that the ability to complete fatty acid (FA) oxidation in the skeletal muscle around parturition decreases, likely due to insufficient metabolic adaptation in response to a load of FA (Yang et al, 2019). In the current study, we hypothesized that an in-depth metabolomic analysis of skeletal muscle would reveal dynamic markers of key regulatory metabolic intermediates, primarily belonging to the muscle lipidome, and would reflect changes in oxidative capacity in the skeletal muscle around calving that are associated with BCS at calving and BCS loss postpartum.…”