TY  - JOUR
AB  - Besides their lipid-digestive role, bile acids (BA) influence overall energy homeostasis, such as glucose and lipid metabolism. We hypothesized that BA along with their receptors, regulatory enzymes, and transporters are present in subcutaneous adipose tissue (scAT). In addition, we hypothesized that their mRNA abundance varies with the body condition of dairy cows around calving. Therefore, we analyzed BA in serum and scAT as well as the mRNA abundance of BA -related enzymes, transporters, and receptors in scAT during the transition period in cows with different body conditions around calving. In a previously established animal model, 38 German Holstein cows were divided into either a high (HBCS; n = 19) or normal BCS (NBCS; n = 19) group based on their body condition score (BCS) and back fat thickness (BFT). Cows were fed different diets to achieve the targeted differences in BCS and BFT (NBCS: BCS <3.5, BFT <1.2 cm; HBCS: BCS >3.75, BFT >1.4 cm) until dry-off at 7 wk ante partum. During the dry period and subsequent lactation, both groups were fed the same diets regarding their demands. Using a targeted metabolomics approach via LC-ESI-MS /MS, BA were analyzed in serum and scAT at wk -7, 1, 3, and 12 relative to parturition. In serum, 15 BA (cholic acid (CA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA), deoxycholic acid (DCA), lithocholic acid (LCA), glycodeoxycholic acid (GDCA), glycolithocholic acid (GLCA), taurodeoxycholic acid (TDCA), taurolithocholic acid (TLCA), β-muricholic acid (MCA(b)), tauromuricholic acid (sum of α and β) (TMCA (a+b)), glycoursodeoxycholic acid (GUDCA)) were observed, whereas in scAT 7 BA (CA, GCA, TCA, GCDCA, TCDCA, GDCA, TDCA) were detected. In serum and scAT samples, the primary BA CA and its conjugate GCA were predominantly detected. Increasing serum concentrations of CA, CDCA, TCA, GCA, GCDCA, DCA, and MCA(b) with the onset of lactation might be related to the increasing DMI after parturition. Furthermore, serum concentrations of CA, CDCA, GCA, DCA, GCDCA, TCA, LCA, and GDCA were lower in HBCS cows compared with NBCS cows, concomitant with increased lipolysis in HBCS cows. The correlation between CA in serum and scAT may point to the transport of CA across cell membranes. Overall, the findings of the present study suggest a potential role of BA in lipid metabolism depending on the body condition of periparturient dairy cows.
AU  - Dicks, L.*
AU  - Schuh-von Graevenitz, K.*
AU  - Prehn, C.
AU  - Sadri, H.*
AU  - Murani, E.*
AU  - Ghaffari, M.H.*
AU  - Häussler, S.*
C1  - 70239
C2  - 55457
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 6288-6307
TI  - Bile acid profiles and mRNA abundance of bile acid-related genes in adipose tissue of dairy cows with high versus normal body condition.
JO  - J. Dairy Sci.
VL  - 107
IS  - 8
PB  - Elsevier Science Inc
PY  - 2024
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - Bile acids (BA) play a crucial role not only in lipid digestion but also in the regulation of overall energy homeostasis, including glucose and lipid metabolism. The aim of this study was to investigate BA profiles and mRNA expression of BA-related genes in the liver of high versus normal body condition in dairy cows. We hypothesized that body condition and the transition from gestation to lactation affect hepatic BA concentrations as well as the mRNA abundance of BA-related receptors, regulatory enzymes, and transporters. Therefore, we analyzed BA in the liver as well as the mRNA abundance of BA-related synthesizing enzymes, transporters, and receptors in the liver during the transition period in cows with different body conditions around calving. In a previously established animal model, 38 German Holstein cows were divided into groups with high body condition score (HBCS; n = 19) or normal body condition score (NBCS; n = 19) based on BCS and backfat thickness (BFT). Cows were fed diets aimed at achieving the targeted differences in BCS and BFT (NBCS: BCS <3.5, BFT <1.2 cm; HBCS: BCS >3.75, BFT >1.4 cm) until they were dried off at wk 7 before parturition. Both groups were fed identical diets during the dry period and subsequent lactation. Liver biopsies were taken at wk −7, 1, 3, and 12 relative to parturition. For BA measurement, a targeted metabolomics approach with liquid chromatography electrospray ionization MS/MS was used to analyze BA in the liver. The mRNA abundance of targeted genes related to BA synthesizing enzymes, transporters, and receptors in the liver was analyzed using microfluidic quantitative PCR. In total, we could detect 14 BA in the liver: 6 primary and 8 secondary BA, with glycocholic acid (GCA) being the most abundant one. The increase of glycine-conjugated BA after parturition, in parallel to increasing serum glycine concentrations may originate from an enhanced mobilization of muscle protein to meet the high nutritional requirements in early lactating cows. Higher DMI in NBCS cows compared with HBCS cows was associated with higher liver BA concentrations such as GCA, deoxycholic acid, and cholic acid. The mRNA abundance of BA-related enzymes measured herein suggests the dominance of the alternative signaling pathway in the liver of HBCS cows. Overall, BA profiles and BA metabolism in the liver depend on both, the body condition and lactation-induced effects in periparturient dairy cows.
AU  - Dicks, L.*
AU  - Schuh-von Graevenitz, K.*
AU  - Prehn, C.
AU  - Sadri, H.*
AU  - Ghaffari, M.H.*
AU  - Häussler, S.*
C1  - 71854
C2  - 56241
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 8688-8708
TI  - Bile acid profiles and messenger RNA expression of bile acid-related genes in the liver of dairy cows with high versus normal body condition.
JO  - J. Dairy Sci.
VL  - 107
IS  - 10
PB  - Elsevier Science Inc
PY  - 2024
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - In the dairy cow, late gestation and early lactation are characterized by a complexity of metabolic processes required for the homeorhetic adaptation to the needs of fetal growth and milk production. Skeletal muscle plays an important role in this adaptation. The objective of this study was to characterize the metabolome in skeletal muscle (semitendinosus muscle) and in serum of dairy cows in the context of the physiological changes occurring in early lactation and to test the effects of dietary supplementation (from d 1 in milk onwards) with conjugated linoleic acids (sCLA; 100 g/d; supplying 7.6 g of cis-9,trans-11 CLA and 7.6 g of trans-10,cis-12 CLA per cow/d; n = 11) compared with control fat-supplemented cows (CTR; n = 10). The metabolome was characterized in skeletal muscle samples collected on d 21 and 70 after calving in conjunction with their serum counterpart using a targeted metabolomics approach (AbsoluteIDQ p180 kit; Biocrates Life Sciences AG, Innsbruck, Austria). Thereby 188 metabolites from 6 different compound classes (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and hexoses) were quantified in both sample types. In both groups, dry matter intake increased after calving. It was lower in sCLA than in CTR on d 21, which resulted in reduced calculated net energy and metabolizable protein balances. On d 21, the concentrations of dopamine, Ala, and hexoses in the skeletal muscle were higher in sCLA than in CTR. On d 21, the changed metabolites in serum were mainly long-chain (>C24) diacyl phosphatidylcholine PC (PC-aa) and acyl-alkyl phosphatidylcholine (PC-ae), along with lysophosphatidylcholine acyl (lysoPC-a) C26:1 that were all lower in sCLA than in CTR. Supplementation with CLA affected the muscle concentrations of 22 metabolites on d 70 including 10 long-chain (>C22) sphingomyelin (SM), hydroxysphingomyelin [SM(OH)], PC-aa, and PC-ae along with 9 long-chain (>C16) lysoPC-a and 3 metabolites related to amino acids (spermine, citrulline, and Asp). On d 70, the concentrations of lysoPC-a C18:2 and C26:0 in serum were higher in the sCLA cows than in the CTR cows. Regardless of treatment, the concentrations of Ile, Leu, Phe, Lys, His, Met, Trp, and hydroxybutyrylcarnitine (C4-OH) decreased, whereas those of ornithine, Gln, and trans-4-hydroxyproline (t4-OH-Pro) increased from d 21 to 70 in muscle. The significantly changed metabolites in serum with time of lactation were 28 long-chain (>C30) PC-ae and PC-aa, 7 long-chain (>C16) SM and SM(OH), along with lysoPC-a C20:3 that were all increased. In conclusion, in addition to other significantly changed metabolites, CLA supplementation mainly led to changes in muscle and serum concentrations of glycerophospholipids and sphingolipids that might reflect the phospholipid compositional changes in muscle. The metabolome changes observed in sCLA on d 21 seem to be, at least in part, due to the lower DMI in these cows. The changes in the muscle concentrations of AA from d 21 to 70, which coincided with the steady energy and MP balances, might reflect a shift of protein synthesis/degradation balance toward synthesis.
AU  - Yang, Y.*
AU  - Sadri, H.*
AU  - Prehn, C.
AU  - Adamski, J.
AU  - Rehage, J.*
AU  - Dänicke, S.*
AU  - Ghaffari, M.H.*
AU  - Sauerwein, H.*
C1  - 61450
C2  - 50257
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 5095-5109
TI  - Targeted assessment of the metabolome in skeletal muscle and in serum of dairy cows supplemented with conjugated linoleic acid during early lactation.
JO  - J. Dairy Sci.
VL  - 104
IS  - 4
PB  - Elsevier Science Inc
PY  - 2021
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - The objective of the current study was to characterize muscle and blood serum acylcarnitine (AcylCN) profiles and to determine the mRNA abundance of muscle carnitine acyltransferases in periparturient dairy cows with high (HBCS) and normal body condition (NBCS). Fifteen weeks antepartum, 38 pregnant multiparous Holstein cows were assigned to 2 groups that were fed differently to reach the targeted BCS and backfat thickness (BFT) until dry-off at -49 d before calving (HBCS: BCS >3.75 and BFT >1.4 cm; NBCS: <3.5 and <1.2 cm). Thereafter, both groups were fed identical diets. Blood samples and biopsies from the semitendinosus muscle were collected on d -49, 3, 21, and 84 relative to calving. Actual BCS at d -49 were 3.02 +/- 0.24 and 3.82 +/- 0.33 (mean +/- SD) for NBCS and HBCS, respectively. In both groups, serum profiles showed marked changes during the periparturient period, with decreasing concentrations of free carnitine and increasing concentrations of long-chain AcylCN. Compared with NBCS, HBCS had greater serum long-chain AcylCN in early lactation, which may point to an insufficient adaptation of their metabolism in response to the metabolic load of fatty acids around parturition. The muscle concentrations of C5-, C9-, C18:1-, and C18:2-AcylCN were lower and those of C14:2-AcylCN were greater in HBCS than in NBCS cows. The mRNA abundance of carnitine palmitoyltransferase (CPT)1, muscle isoform (CPT1b) and CPT2 increased from d -49 to early lactation (d 3, d 21), followed by a decline to nearly antepartum values by d 84; this change was not affected by group. In conclusion, over-conditioning around calving seems to be associated with mitochondrial overload, which can result in incomplete fatty acid oxidation in dairy cows.
AU  - Ghaffari, M.H.*
AU  - Sadri, H.*
AU  - Schuh, K.*
AU  - Dusel, G.*
AU  - Prehn, C.
AU  - Adamski, J.
AU  - Koch, C.*
AU  - Sauerwein, H.*
C1  - 58534
C2  - 48496
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 4777-4794
TI  - Alterations of the acylcarnitine profiles in blood serum and in muscle from periparturient cows with normal or elevated body condition.
JO  - J. Dairy Sci.
VL  - 103
IS  - 5
PB  - Elsevier Science Inc
PY  - 2020
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - The transition from late gestation to early lactation is associated with extensive changes in metabolic, endocrine, and immune functions in dairy cows. Skeletal muscle plays an important role in maintaining the homeorhetic adaptation to the metabolic needs of lactation. The objective of this study was to characterize the skeletal muscle metabolome in the context of the metabolic changes that occur during the transition period in dairy cows with high (HBCS) versus normal body condition (NBCS). Fifteen weeks antepartum, 38 pregnant multiparous Holstein cows were assigned to 1 of 2 groups, which were fed differently to reach the targeted BCS and back fat thickness (BFT) until dry-off at -49 d before calving (HBCS: >3.75 and >1.4 cm; NBCS: <3.5 and <1.2 cm). During the dry period and the subsequent lactation, both groups were fed identical diets. The differences in both BCS and BFT were maintained throughout the study. The metabolome was characterized in skeletal muscle samples (semitendinosus muscle) collected on d -49, 3, 21, and 84 relative to calving using a targeted metabolomics approach (AbsolutelDQ p180 kit; Biocrates Life Sciences AG, Innsbruck, Austria), which allowed for the quantification of up to 188 metabolites from 6 different compound classes (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and hexoses). On d -49, the concentrations of citrulline and hydroxytetradecadienyl-L-carnitine in muscle were higher in HBCS cows than in NBCS cows, but those of carnosine were lower. Over-conditioning did not affect the muscle concentrations of any of the metabolites on d 3. On d 21, the concentrations of phenylethylamine and linoleylcarnitine in muscle were lower in HBCS cows than in NBCS cows, and the opposite was true for lysophosphatidylcholine acyl C20:4. On d 84, the significantly changed metabolites were mainly long-chain (>C32) acyl-alkyl phosphatidylcholine and di-acyl phosphatidylcholine, along with 3 long-chain (>C16) sphingomyelin that were all lower in HBCS cows than in NBCS cows. These data contribute to a better understanding of the metabolic adaptation in skeletal muscle of dairy cows during the transition period, although the physiological significance and underlying molecular mechanisms responsible for the regulation of citrulline, hydroxytetradecadienyl-L-carnitine, carnosine, and phenylethylamine associated with over-conditioning are still elusive and warrant further investigation. The changes observed in muscle lysophosphatidylcholine and phosphatidylcholine concentrations may point to an alteration in phosphatidylcholine metabolism, probably resulting in an increase in membrane stiffness, which may lead to abnormalities in insulin signaling in the muscle of over-conditioned cows.
AU  - Sadri, H.*
AU  - Ghaffari, M.H.*
AU  - Schuh, K.*
AU  - Dusel, G.*
AU  - Koch, C.*
AU  - Prehn, C.*
AU  - Adamski, J.
AU  - Sauerwein, H.*
C1  - 58101
C2  - 48203
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 3730-3744
TI  - Metabolome profiling in skeletal muscle to characterize metabolic alterations in over-conditioned cows during the periparturient period.
JO  - J. Dairy Sci.
VL  - 103
IS  - 4
PB  - Elsevier Science Inc
PY  - 2020
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - The mammalian target of rapamycin (mTOR) is a major regulator of protein synthesis via its main down-stream effectors, ribosomal protein S6 kinase (S6K1) and eukaryotic initiation factor 4E binding protein (4EBP1). The ubiquitin-proteasome system (UPS) is the main proteolytic pathway in muscle, and the muscle-specific ligases tripartite motif containing 63 (TRIM63; also called muscle-specific ring-finger protein 1, MuRF-1) and F-box only protein 32 (FBXO32; also called atrogin-1) are important components of the UPS. We investigated 20S proteasome activity and mRNA expression of key components of mTOR signaling and UPS in skeletal muscle of dairy cows during late gesta-tion and early lactation and tested the effects of dietary supplementation (from d 1 in milk) with conjugated linoleic acids (sCLA; 100 g/d; n = 11) compared with control fat-supplemented cows (CTR; n = 10). Blood and muscle tissue (semitendinosus) samples were col- lected on d 1, 21, and 70 relative to parturition. Dry matter intake increased with time of lactation in both groups. It was lower in sCLA than in CTR on d 21, which resulted in a reduced calculated metaboliz-able protein balance. Most serum and muscle concen-trations of AA followed time-related changes but were unaffected by CLA supplementation. In both groups, serum and muscle 3-methylhistidine (3-MH) concentrar tions and the ratio of 3-MH:creatinine increased from d -21 to d 1, followed by a decline on d 21. The mRNA abundance of MTOR on d 21 and 70 was greater in sCLA than in CTR. The abundance of 4EBP1 mRNA did not differ between groups but was upregulated in both on d 1. The mRNA abundance of SOK1 on d 70 was greater in CTR than in sCLA, but remained unchanged over time in both groups. The mRNA abundance of FBXOS2 (encoding atrogin-1) on d 21 was greater in sCLA than in CTR. The mRNA abundance of TRIM63 (also known as MuRF1) showed a similar pattern as FBXO32 in both groups: an increase from d -21 to d 1, followed by a decline. The mRNA for the alpha (BCKDHA) and beta (BCKDHB) polypeptide of branched-chain a-keto acid dehydrogenase was elevated in sCLA and CTR cows on d 21, respectively, suggesting a role of CLA in determining the metabolic fate of branched-chain AA. For the mTOR protein, no group differences were observed. The abundance of 56K1 protein was greater across all time points in sCLA versus CTR. The antepartum 20S proteasome activity in muscle was elevated in both groups compared with postpartum, probably reflecting the start of protein mobilization before parturition. Plasma insulin concentrations decreased in both groups postpartum but to a greater extent in CTR than in sCLA, resulting in greater insulin concentrations in sCLA than in CTR. Thus, the greater abundance of MTOR mRNA and S6K1 protein in sCLA compared with CTR might be mediated by the greater plasma insulin postpartum. The upregulation of MTOR mRNA in sCLA cows on d 21, despite greater PBxon mRNA abundance, may reflect a simultaneous activation of both anabolic and catabolic signaling pathways, likely resulting in greater protein turnover.
AU  - Yang, Y.*
AU  - Sadri, H.*
AU  - Prehn, C.
AU  - Adamski, J.
AU  - Rehage, J.*
AU  - Dänicke, S.*
AU  - von Soosten, D.*
AU  - Metges, C.C.*
AU  - Ghaffari, M.H.*
AU  - Sauerwein, H.*
C1  - 58726
C2  - 48261
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 2829-2846
TI  - Proteasome activity and expression of mammalian target of rapamycin signaling factors in skeletal muscle of dairy cows supplemented with conjugated linoleic acids during early lactation.
JO  - J. Dairy Sci.
VL  - 103
IS  - 3
PB  - Elsevier Science Inc
PY  - 2020
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - Biogenic amines (BA) are a class of nitrogenous compounds that are involved in a wide variety of physiological processes, but their role in transition cows is poorly understood. Our objectives were to describe the longitudinal changes of BA in serum and in skeletal muscle during the transition period and to characterize temporal responses of BA in relation to body condition score (BCS) of periparturient dairy cows. Fifteen weeks before calving, 36 multiparous Holstein cows were assigned to 2 groups (n = 18 per group) that were fed differently to reach either high [HBCS; net energy for lactation (NEL) = 7.2 MJ/kg of dry matter (DM)] or normal BCS (NBCS; NEL- 6.8 MJ/kg of DM) at dry-off. The targeted BCS and back fat thickness (BFT) at dry-off (HBCS, >3.75 and >1.4 cm; NBCS, <3.5 and <1.2 cm) were reached. Thereafter, both groups were fed identical diets. Blood samples and muscle (semitendinosus) biopsies were collected at d 49, +3, +21, and +84 relative to parturition. In serum and skeletal muscle, BA concentrations were measured using a targeted metabolomics assay. The data were analyzed as a repeated measure using the MIXED procedure of SAS. The serum concentrations of most BA (i.e., creatinine, taurine, carnosine putrescine, spermine, alpha-aminoadipic acid, acetylornithine, kynurenine, serotonin, hydroxyproline, asymmetric dimethylarginine, and symmetric dimethylarginine) fluctuated during the transition period, while others (i.e., spermidine, phenylethylarnine) did not change with time. The muscle concentrations of BA remained unchanged over time. Creatinine had the highest concentrations in the serum, while carnosine had the highest concentration among the muscle BA. The serum concentrations of creatinine (d +21), putrescine (d +84), alpha-aminoadipic acid (d +3), and hydroxyproline (d +21) were or tended to be higher for HBCS compared with NBCS postpartum. The serum concentrations of symmetric dimethylarginine (d -49) and acetylornithine (d +84) were or tended to be lower for HBCS compared with NBCS, respectively. The serum kynurenine/tryptophan ratio was greater with HBCS than with NBCS (d +84). Compared with NBCS, HBCS was associated with lower muscle concentrations of carnosine, but those of hydroxyproline were higher (d -49). In both serum and muscle, the asymmetric dimethylarginine concentrations were greater with HBCS than with NBCS (d -49). No correlation was found between serum and skeletal muscle BA. This study indicates that overconditioning of dairy cows may influence serum and muscle BA concentrations in the periparturient period.
AU  - Ghaffari, M.H.*
AU  - Sadri, H.*
AU  - Schuh, K.*
AU  - Dusel, G.*
AU  - Frieten, D.*
AU  - Koch, C.*
AU  - Prehn, C.
AU  - Adamski, J.
AU  - Sauerwein, H.*
C1  - 55985
C2  - 46690
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 6571-6586
TI  - Biogenic amines: Concentrations in serum and skeletal muscle from late pregnancy until early lactation in dairy cows with high versus normal body condition score.
JO  - J. Dairy Sci.
VL  - 102
IS  - 7
PB  - Elsevier Science Inc
PY  - 2019
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - This study aimed to investigate the differences in the metabolic profiles in serum of dairy cows that were normal or overconditioned when dried off for elucidating the pathophysiological reasons for the increased health disturbances commonly associated with overconditioning. Fifteen weeks antepartum, 38 multiparous Holstein cows were allocated to either a high body condition (HBCS; n = 19) group or a normal body condition (NBCS; n = 19) group and were fed different diets until dry-off to amplify the difference. The groups were also stratified for comparable milk yields (NBCS: 10,361 +/- 302 kg; HBCS: 10,315 +/- 437 kg; mean +/- standard deviation). At dry-off, the cows in the NBCS group (parity: 2.42 +/- 1.84; body weight: 665 +/- 64 kg) had a body condition score (BCS) <3.5 and backfat thickness (BFT) <1.2 cm, whereas the HBCS cows (parity: 3.37 +/- 1.67; body weight: 720 +/- 57 kg) had BCS >3.75 and BFT >1.4 cm. During the dry period and the subsequent lactation, both groups were fed identical diets but maintained the BCS and BFT differences. A targeted metabolomics (AbsoluteIDQ p180 kit, Biocrates Life Sciences AG, Innsbruck, Austria) approach was performed in serum samples collected on d -49, +3, +21, and +84 relative to calving for identifying and quantifying up to 188 metabolites from 6 different compound classes (acylcarnitines, AA, biogenic amines, glycerophospholipids, sphingolipids, and hexoses). The concentrations of 170 metabolites were above the limit of detection and could thus be used in this study. We used various machine learning (ML) algorithms (e.g., sequential minimal optimization, random forest, alternating decision tree, and naive Bayes-updatable) to analyze the metabolome data sets. The performance of each algorithm was evaluated by a leave-one-out cross-validation method. The accuracy of classification by the ML algorithms was lowest on d 3 compared with the other time points. Various ML methods (partial least squares discriminant analysis, random forest, information gain ranking) were then performed to identify those metabolites that were contributing most significantly to discriminating the groups. On d 21 after parturition, 12 metabolites (acetylcarnitine, hexadecanoyl-carnitine, hydroxyhexadecenoyl-carnitine, octadecanoyl-carnitine, octadecenoyl-carnitine, hydroxybutyryl-carnitine, glycine, leucine, phosphatidylcholine-diacyl-C40:3, trans-4-hydroxyproline, carnosine, and creatinine) were identified in this way. Pathway enrichment analysis showed that branched-chain AA degradation (before calving) and mitochondrial beta-oxidation of long-chain fatty acids along with fatty acid metabolism, purine metabolism, and alanine metabolism (after calving) were significantly enriched in HBCS compared with NBCS cows. Our results deepen the insights into the phenotype related to overconditioning from the preceding lactation and the pathophysiological sequelae such as increased lipolysis and ketogenesis and decreased feed intake.
AU  - Ghaffari, M.H.*
AU  - Jahanbekam, A.*
AU  - Sadri, H.*
AU  - Schuh, K.*
AU  - Dusel, G.*
AU  - Prehn, C.
AU  - Adamski, J.
AU  - Koch, C.*
AU  - Sauerwein, H.*
C1  - 56954
C2  - 47456
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 11561-11585
TI  - Metabolomics meets machine learning: Longitudinal metabolite profiling in serum of normal versus overconditioned cows and pathway analysis.
JO  - J. Dairy Sci.
VL  - 102
IS  - 12
PB  - Elsevier Science Inc
PY  - 2019
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - The objective of the current study was to investigate the effects of overconditioning around calving on gene expression of key components of the mammalian target of rapamycin (mTOR) pathway and ubiquitin-proteasome system (UPS) in skeletal muscle as well as the AA profiles in both serum and muscle of periparturient cows. Fifteen weeks antepartum, 38 multiparous Holstein cows were allocated to either a high body condition group (HBCS; n = 19) or a normal body condition group (NBCS; n = 19) and were fed different diets until dry-off (d -49 relative to calving) to amplify the difference. The groups were also stratified for comparable milk yields (NBCS: 10,361 +/- 302 kg; HBCS: 10,315 +/- 437 kg). At dry-off, the NBCS cows (parity: 2.42 +/- 1.84; body weight: 665 +/- 64 kg) had a body condition score (BCS) <3.5 and backfat thickness (BFT) <1.2 cm, whereas the HBCS cows (parity: 3.37 +/- 1.67; body weight: 720 +/- 57 kg) had a BCS >3.75 and BFT >1.4 cm. During the dry period and the subsequent lactation, both groups were fed identical diets but maintained the BCS and BFT differences. Blood samples and skeletal muscle biopsies (semitendinosus) were repeatedly (d -49, +3, +21, and +84 relative to calving) collected for assessing the concentrations of free AA and the mRNA abundance of various components of mTOR and UPS. The differences in BCS and BFT were maintained throughout the study. The circulating concentrations of most AA with the exception of Gly, Gin, Met, and Phe increased in early lactation in both groups. The serum concentrations of Ala (d +21 and -184) and Orn (d +84) were lower in HBCS cows than in NBCS cows, but those of Gly, His, Leu, Val, Lys, Met, and Orn on d -49 and Ile on d +21 were greater in HBCS cows than in NBCS cows. The serum concentrations of 3-methylhistidine, creatinine, and 3-methylhistidine:creatinine ratio increased after calving (d +3) but did not differ between the groups. The muscle concentrations of all AA (except for Cys) remained unchanged over time and did not differ between groups. The muscle concentrations of Cys were greater on d -49 but tended to be lower on d +21 in HBCS cows than in NBCS cows. On d +21, TrITOR and eukaryotic translation initiation factor 4E binding protein 1 mRNA abundance was greater in HBCS cows than in NBCS cows, whereas ribosomal protein S6 kinase 1 was not different between the groups. The mRNA abundance of ubiquitin-activating enzyme 1 (d +21), ubiquitin-conjugating enzyme 1 (d +21), atrogin-1 (d +21), and ring finger protein-1 (d +3) enzymes was greater in HBCS cows than in NBCS cows, whereas ubiquitin-conjugating enzyme 2 was not different between the groups. The increased mRNA abundance of key components of mTOR signaling and of muscle-specific ligases of HBCS cows may indicate a simultaneous activation of anabolic and catabolic processes and thus increased muscle protein turnover, likely as a part of the adaptive response to prevent excessive loss of skeletal muscle mass during early lactation.
AU  - Ghaffari, M.H.*
AU  - Schuh, K.*
AU  - Dusel, G.*
AU  - Frieten, D.*
AU  - Koch, C.*
AU  - Prehn, C.
AU  - Adamski, J.
AU  - Sauerwein, H.*
AU  - Sadri, H.*
C1  - 57023
C2  - 47480
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 11544-11560
TI  - Mammalian target of rapamycin signaling and ubiquitin-proteasome-related gene expression in skeletal muscle of dairy cows with high or normal body condition score around calving.
JO  - J. Dairy Sci.
VL  - 102
IS  - 12
PB  - Elsevier Science Inc
PY  - 2019
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - Acylcarnitines (ACC) are formed when fatty acid (FA)-coenzyme A enters the mitochondria for beta-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 beta-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-1.0,6.942 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 muscle were 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 (CPT/B) 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.
AU  - Yang, Y.*
AU  - Sadri, H.*
AU  - Prehn, C.
AU  - Adamski, J.
AU  - Rehage, J.*
AU  - Dänicke, S.*
AU  - Saremi, B.*
AU  - Sauerwein, H.P.*
C1  - 54564
C2  - 45642
CY  - 360 Park Ave South, New York, Ny 10010-1710 Usa
SP  - 754-767
TI  - Acylcarnitine profiles in serum and muscle of dairy cows receiving conjugated linoleic acids or a control fat supplement during early lactation.
JO  - J. Dairy Sci.
VL  - 102
IS  - 1
PB  - Elsevier Science Inc
PY  - 2019
SN  - 0022-0302
ER  - 

TY  - JOUR
AB  - Left-sided displacement of the abomasum (LDA) is one of the most common disorders of the digestive system in many dairy breeds and particularly in Holstein dairy cows. We performed a genome-wide association study for 854 German Holstein cows, including 225 cases and 629 controls. All cows were genotyped using the Illumina Bovine SNP50 Bead Chip (Illumina Inc., San Diego, CA). After quality control of genotypes, a total of 36,226 informative single nucleotide polymorphisms (SNP) were left for analysis. We used a mixed linear model approach for a genome-wide association study of LDA. In total, 36 SNP located on 17 bovine (Bos taurus) chromosomes (BTA) showed associations with LDA at nominal -log(10) P-values >3.0. Two of these SNP, located on BTA11 at 46.70 Mb and BTA20 at 16.67 Mb, showed genome-wide significant associations with LDA at -log(10) P-values >4.6. Pathway analyses indicated genes involved in calcium metabolism and insulin-dependent diabetes mellitus to be factors in the pathogenesis of LDA in German Holstein cows.
AU  - Mömke, S.*
AU  - Sickinger, M.*
AU  - Lichtner, P.
AU  - Doll, K.*
AU  - Rehage, J.*
AU  - Distl, O.*
C1  - 24866
C2  - 31737
SP  - 3959-3964
TI  - Genome-wide association analysis identifies loci for left-sided displacement of the abomasum in German Holstein cattle.
JO  - J. Dairy Sci.
VL  - 96
IS  - 6
PB  - Elsevier Science
PY  - 2013
SN  - 0022-0302
ER  -