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

Ghaffari, Mohtasham; Schuh, Katharina; Dusel, G.; Frieten, D.; Koch, Christian; Prehn, Cornelia; Adamski, Jerzy; Sauerwein, H.; Sadri, H.

doi:10.3168/jds.2019-17130

Cited by 11 publications

(9 citation statements)

References 90 publications

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“…In the current study, concentrations of proteinogenic AA (except for histidine) in muscle remained fairly constant throughout the observation period despite, as reported previously (Ghaffari et al, 2019b), a concomitant decline in serum levels. The reason for these observations is not clear, but it is likely that muscle has increased transport activity to offset the decline in serum concentrations and thus maintain intracellular concentrations of the respective AA, assuming measurement at a single time point is reflective of the steady state.…”

Section: Discussionsupporting

confidence: 89%

“…Thus, as part of a physiological regulatory process, skeletal muscle that synthesizes carnosine can also release it into the circulation, probably through dipeptide transporters, to supply the needs of other tissues where it can be degraded or used (e.g., for delivery of l-histidine or β-alanine; Boldyrev, 2012). The finding that not only carnosine but also serum histidine concentrations were greater in HBCS cows on d −49 (Ghaffari et al, 2019b), may indicate 3). The pink circles show metabolites that were significantly changed and the gray circles show metabolites that were not significantly changed.…”

Section: Discussionmentioning

confidence: 99%

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

Sadri

Ghaffari

Schuh

et al. 2020

Journal of Dairy Science

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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 (AbsoluteIDQ 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.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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

Sadri

Ghaffari

Schuh

et al. 2020

Journal of Dairy Science

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“…The observed differences in pre-and postpartum BCS and BW between the 2 groups (HBCS: prepartum 3.77 ± 0.08 and 810 ± 28 kg, postpartum 3.30 ± 0.06 and 674 ± 11 kg; NBCS: prepartum 3.16 ± 0.06 and 715 ± 25 kg, postpartum 2.89 ± 0.06 and 631 ± 12 kg) would clearly be in favor of this. Further data collected from the same study population as used herewith indicate that high BCS and BFT were associated with a greater mRNA abundance of the 2 muscle-specific ligases muscle RING finger protein-1 (MuRF-1) and atrogin-1 (Ghaffari et al, 2019), and consequently, a more stimulated proteolysis in these cows seems likely. Over-conditioned cows might then also have a greater reservoir of BCAA and counteractively a higher tissue abundance of BCAA degrading enzymes.…”

Section: Discussionmentioning

confidence: 73%

Branched-chain amino acids: Abundance of their transporters and metabolizing enzymes in adipose tissue, skeletal muscle, and liver of dairy cows at high or normal body condition

Webb

Sadri

Schuh

et al. 2020

Journal of Dairy Science

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Branched-chain amino acids (BCAA) are major components of milk protein and important precursors for nonessential AA. Thus, the BCAA transport and break-down play a key role in the metabolic adaptation to the high nutrient demands in lactation. However, in monogastrics, increased BCAA levels have been linked with obesity and certain metabolic disorders such as impaired insulin sensitivity. Our objective was to study the effect of over-conditioning at calving on plasma BCAA levels as well as the tissue abundance of the most relevant BCAA transporters and degrading enzymes in dairy cows during late pregnancy and early lactation. Thirty-eight Holstein cows were allocated 15 wk antepartum to either a normal-(NBCS) or overconditioned (HBCS) group, receiving 6.8 or 7.2 MJ of NE L /kg of DM, respectively, during late lactation to reach the targeted differences in body condition score (BCS) and back fat thickness (BFT; NBCS: BCS <3.5, BFT <1.2 cm; HBCS: BCS >3.75, BFT >1.4 cm) until dry-off. During the dry period and next lactation, cows were fed the same diets, whereby differences in BCS and BFT were maintained: prepartum means were 3.16 ± 0.06 and 1.03 ± 0.07 cm (NBCS) vs. 3.77 ± 0.08 and 1.89 ± 0.11 cm (HBCS), postpartum means were 2.89 ± 0.06 and 0.81 ± 0.05 cm (NBCS) vs. 3.30 ± 0.06 and 1.38 ± 0.08 cm (HBCS). Blood and biopsies from liver, semitendinosus muscle, and subcutaneous adipose tissue (scAT) were sampled at d 49 antepartum, 3, 21, and 84 postpartum. Free BCAA were analyzed and the mRNA abundance of solute carrier family 1 member 5 (SLC1A5), SLC7A5, and SLC38A2 as well as branchedchain aminotransferase 2 (BCAT2), branched-chain α-keto acid dehydrogenase E1α (BCKDHA), and branched-chain α-keto acid dehydrogenase E1β (BCK-DHB) as well as the protein abundance of BCKDHA were assessed. Concentrations of all BCAA changed with time, most markedly in HBCS cows, with a nadir around calving. Apart from Ile, neither individual nor total BCAA differed between groups. The HBCS group had greater BCKDHA mRNA as well as higher prepartum BCKDHA protein abundance in scAT than NBCS cows, pointing to a greater oxidative capacity for the irreversible degradation of BCAA transamination products in scAT of over-conditioned cows. Prepartum hepatic BCKDHA protein abundance was lower in HBCS than in NBCS cows. In both groups, SLC1A5, SLC7A5, and BCAT2 mRNA were most abundant in scAT, whereas SLC38A2 was higher in scAT and muscle compared with liver, and BCKDHA and BCKDHB mRNA were greatest in liver and muscle, respectively. Our results indicate that scAT may be a major site of BCAA uptake and initial catabolism, with the former, however, being independent of BCS and time relative to calving in dairy cows.

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“…Previous studies have shown that cows with greater oxidative stress have a greater abundance of proteins involved in the ubiquitin proteasome pathway [27]. This pathway is responsible for removing toxins and recycling wastes from cells and tissues.…”

Section: Discussionmentioning

confidence: 99%

Impact of Exposure to Chronic Light–Dark Phase Shifting Circadian Rhythm Disruption on Muscle Proteome in Periparturient Dairy Cows

2021

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Muscle tissue serves as a key nutrient reservoir that dairy cows utilize to meet energy and amino acid requirements for fetal growth and milk production. Circadian clocks act as homeostatic regulators so that organisms can anticipate regular environmental changes. The objective of this study was to use liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine how chronic circadian disruption in late gestation affected the muscle tissue proteome. At five weeks before expected calving (BEC), multiparous Holstein cows were assigned to either a control (CON, n = 8) or a 6 h forward phase shift (PS, n = 8) of the light–dark cycle every 3 days. At calving, all animals were exposed to CON light–dark cycles. Muscle biopsies were collected from longissimus dorsi muscles at 21 days BEC and at 21 days postpartum (PP). At p < 0.1, 116 and 121 proteins were differentially abundant between PS and CON at 21 days BEC and 21 days PP, respectively. These proteins regulate beta oxidation and glycolysis. Between pregnancy and lactation, 134 and 145 proteins were differentially abundant in CON and PS cows, respectively (p < 0.1). At both timepoints, PS cows exhibited an oxidative stress signature. Thus, dairy cattle management strategies that minimize circadian disruptions may ensure optimal health and production performance.

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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

Cited by 11 publications

References 90 publications

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

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

Branched-chain amino acids: Abundance of their transporters and metabolizing enzymes in adipose tissue, skeletal muscle, and liver of dairy cows at high or normal body condition

Impact of Exposure to Chronic Light–Dark Phase Shifting Circadian Rhythm Disruption on Muscle Proteome in Periparturient Dairy Cows

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