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

Abstract

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.

Molecular networks of insulin signaling and amino acid metabolism in subcutaneous adipose tissue are altered by body condition in periparturient Holstein cows

“…Our previous work also confirmed that neutral AA (SLC1A5), BCAA (SLC7A5), and SLC38A1 transporters are expressed in bovine SAT (Liang et al, 2019). In addition, compared with liver and skeletal muscle, bovine SAT has the greatest mRNA abundance of the BCAA transporters SLC1A5 and SLC7A5, and branched-chain aminotransferase 2 (Webb et al, 2020). Thus, available data suggest that AA uptake and metabolism in SAT are important aspects of tissue metabolism.…”

Multifaceted role of one-carbon metabolism on immunometabolic control and growth during pregnancy, lactation and the neonatal period in dairy cattle

“…Data in the graphs are split between cows receiving Met and those that did not receive Met pathway [124]. Of note, a recent study reported that compared with liver and skeletal muscle, SAT had the greatest mRNA abundance of enzymes associated with branched chain AA catabolism in peripartal cows [125]. Thus, due to inherent differences in AA metabolism among tissues, it is likely that Met might play different roles across tissues during the transition period.…”

Branched-Chain Amino Acid Supplementation Alters the Abundance of Mechanistic Target of Rapamycin and Insulin Signaling Proteins in Subcutaneous Adipose Explants from Lactating Holstein Cows

“…Alterations in the abundance of plasma membrane AA transporters and extracellular sensors of AA availability can also control BCAA metabolism, including signaling via mTORC1 [ 22 ]. Emerging evidence also indicates that adipose tissue might be a target organ for BCAA metabolism in dairy cows [ 8 ].…”

“…The recent demonstration via metabolomics analysis that a high body condition score is associated with greater BCAA degradation before calving [ 7 ] suggested there is a potential relationship between body fat and BCAA metabolism in dairy cows. Although bovine adipose tissue has not been generally considered responsive to AA supply, recent research indicated that, compared with liver and skeletal muscle, the s.c. adipose tissue (SAT) in dairy cows has the greatest mRNA abundance of mitochondrial branched-chain aminotransferase ( BCAT2 ) [ 8 ]; furthermore, BCAA, Gln, and neutral AA transporters are expressed in bovine SAT [ 8 , 9 ]. Hence, available data support the notion that bovine SAT is a potential site for BCAA uptake and metabolism.…”