Graduate Student Literature Review: Exploring choline's important roles as a nutrient for transition dairy cows.

In late gestation and in the first weeks postpartum, lipid droplets accumulate in the hepatic tissue resulting in approximately 40% to 50% of the dairy cows developing hepatic lipidosis in the first weeks of lactation. Elevated concentrations of triacylglycerol in the hepatic tissue are associated with increased risk of peripartum diseases and impaired productive performance. Cows with hepatic lipidosis need to dispose the excess of hepatic triacylglycerol, but this is a slow process in the bovine liver and relies on primary mechanisms such as complete oxidation and ketogenesis because of the limited export of triacylglycerols as lipoproteins. Choline is a lipotropic compound because, among other functions, it facilitates the export of lipids from the liver. Supplementing choline as rumen-protected choline (RPC) to diets of feed-restricted dairy cows reduces the degree of triacylglycerol infiltration into the hepatic parenchyma in part by enhancing export of triacylglycerol as nascent lipoprotein. The reduced accumulation of triacylglycerol in hepatic tissue in feed-restricted cows fed RPC might affect secondary pathways involved in hepatic disposal of fatty acids such as increased cellular autophagy and lipophagy and minimize endoplasmic reticulum stress response and hepatocyte inflammation. Collectively, these effects on secondary pathways might further reduce the severity of hepatic lipidosis in cows. One of the benefits of supplementing RPC is improved fat digestibility, perhaps because choline, through phosphatidylcholines, facilitates lipid transport within the enterocyte by increasing the synthesis of chylomicrons. Finally, when supplemented during the transition period, RPC improves productive performance of cows, irrespective of their body condition, that extends well beyond the period of supplementation. This review summarizes the current understanding of hepatic lipidosis in early lactation, recapitulates the absorption, transport and metabolism of choline, and discusses its role on hepatic metabolism and gastrointestinal functions, which collectively results in improved performance in dairy cows.

Effects of feeding rumen-protected lysine during the postpartum period on performance and amino acid profile in dairy cows: A meta-analysis.

Lysine is one of the limiting AA in the diets of dairy cows and is typically fed as rumen-protected Lys (RPL). We hypothesized that supplementation of RPL during the postpartum period would improve the productive performance in dairy cows. Objectives were to use meta-analytic methods to explore the effects of feeding RPL on performance and blood AA profile in lactating dairy cows. An additional objective was to identify an optimal concentration (%) of Lys in MP (LYSMP) and determine if responses to LYSMP were associated with the concentration (%) of Met in MP (METMP). The literature was systematically reviewed, and 13 experiments, comprising 40 treatment means and 594 lactating cows, were included in the meta-analysis. All experiments had a nonsupplemental control (CON; n = 17 treatment means), or a group supplemented with RPL (n = 23 treatment means). Cows supplemented with RPL were supplied additionally with a mean (±standard deviation) 19.3 ± 10.3 g/d metabolizable Lys (5.1-40.6 g/d). Meta-analytical statistics were used to estimate the weighted mean difference in STATA. Mixed models were fitted to the data to investigate the linear and quadratic effects of LYSMP, METMP, and interactions between LYSMP and METMP. All models included the random effect of experiment and weighting by the inverse of the SE of the means squared. Cows that began receiving RPL in early lactation (≤90 DIM) or for an extended duration (≥70 DIM) produced 1.51 kg/d more milk compared with CON cows. Increasing digestible LYSMP from 6.5% to 8.5% linearly increased yields of milk, FCM, ECM, and milk fat by 1.8, 2.5, 2.4, and 0.10 kg/d, respectively, and tended to increase milk protein yield and body weight gain by 0.07 and 0.09 kg/d, respectively, without a concurrent increase in DMI. Interactions between the linear effects of LYSMP and METMP were observed for FCM/DMI or ECM/DMI. In a diet with low METMP (e.g., 1.82% of MP), a digestible supply of 7.40% LYSMP would result in 1.46 and 1.47 kg/kg FCM/DMI or ECM/DMI, respectively; however, with high digestible METMP (e.g., 2.91% of MP), supplying 7.40% of digestible LYSMP would result in 1.68 and 1.62 kg/kg FCM/DMI or ECM/DMI, respectively. Increasing digestible LYSMP from 6.5% to 8.5% linearly increased blood concentrations of Lys by 16.6 µM, whereas blood concentrations of Met and Ala decreased by 4.6 and 6.0 µM, respectively. Nevertheless, an interaction was also observed between LYSMP and METMP for blood concentrations of total EAA because as METMP increased, the positive response to LYSMP on total EAA was also increased, suggesting a competitive mobilization of AA and their utilization in various body tissues. Only 4 out of the 13 experiments in this meta-analysis involved primiparous cows; thus, insufficient data were available to understand the role of supplemental RPL in primiparous cows. Collectively, feeding RPL improved productive performance, and the increments were maximized up to 9.25% of LYSMP in multiparous dairy cows.

Rumen-protected choline reduces hepatic lipidosis by increasing hepatic triacylglycerol-rich lipoprotein secretion in dairy cows.

Objectives were to determine the effects of supplementing rumen-protected choline (RPC) on hepatic composition and secretion of triacylglycerol-rich lipoprotein when cows were subjected to feed restriction to develop fatty liver. It was hypothesized that RPC reduces hepatic triacylglycerol by enhancing secretion of hepatic lipoprotein. Pregnant, nonlactating parous Holstein cows (n = 33) at mean (± standard deviation) 234 ± 2.2 d of gestation were blocked by body condition (3.79 ± 0.49) and assigned to receive 0 g/d (CON), 25.8 g/d choline ion from a RPC product containing 28.8% choline chloride (CC; treatment L25.8), or 25.8 g/d of choline ion from a RPC product containing 60.0% CC (H25.8). Cows were fed for ad libitum intake for the first 5 d and restricted to 41% of the net energy for lactation required for maintenance and pregnancy from d 6 to 13. Intake of metabolizable methionine was maintained at 18 g/d during feed restriction by supplying rumen-protected methionine. Hepatic tissue was sampled on d 6 and 13 and analyzed for triacylglycerol and glycogen, and mRNA expression of hepatic tissue was investigated. On d 14, cows were not fed and received a 10% solution of tyloxapol intravenously at 120 mg/kg of body weight to block hydrolysis of triacylglycerols in very low density lipoprotein (VLDL). Blood was sampled sequentially for 720 min and analyzed for concentration of triacylglycerol and total cholesterol. Lymph was sampled 6 h after tyloxapol infusion, and analyzed for concentrations of fatty acids, ß-hydroxybutyrate, glucose, triacylglycerol, and total cholesterol. A sample of serum collected at 720 min after tyloxapol was assayed for the metabolome composition. The area under the curve (AUC) of serum triacylglycerol, VLDL cholesterol, and total cholesterol were calculated. Orthogonal contrasts evaluated the effect of supplementing RPC (CON vs. [1/2 L25.8 + 1/2 H25.8]) and source of RPC (L25.8 vs. H25.8). Least squares means and standard errors of the means are presented in sequence as CON, L25.8, H25.8. During feed restriction, supplementation of RPC reduced hepatic triacylglycerol (9.0 vs. 4.1 vs. 4.5 ± 0.6%) and increased glycogen contents (1.9 vs. 3.5 vs. 4.1 ± 0.2%). Similarly, supplementation of RPC increased the expression of transcripts involved in the synthesis and assembly of lipoproteins (MTTP), cellular autophagy (ATG3), and inflammation (TNFA), and reduced the expression of transcripts associated with mitochondrial oxidation of fatty acids (HADHA, MLYCD) and stabilization of lipid droplets (PLIN2). After infusion of tyloxapol, RPC increased the AUC for serum triacylglycerol (21,741 vs. 32,323 vs. 28,699 ± 3,706 mg/dL × min) and VLDL cholesterol (4,348 vs. 6,465 vs. 5,740 ± 741 mg/dL × min) but tended to reduce the concentrations of triacylglycerol in lymph (16.7 vs. 13.8 vs. 11.9 ± 1.9 mg/dL). Feeding RPC tended to increase the concentrations of 89 metabolites in serum, after adjusting for false discovery, including 3 acylcarnitines, 1 AA-related metabolite, 11 bile acids, 1 ceramide, 6 diacylglycerols, 2 dihydroceramides, 1 glycerophospholipid, and 64 triacylglycerols compared with CON. Feeding 25.8 g/d of choline ion as RPC mediated increased hepatic triacylglycerol secretion to promote lipotropic effects that reduced hepatic lipidosis in dairy cows.

Effect of source and amount of rumen-protected choline on hepatic metabolism during induction of fatty liver in dairy cows.

Objectives were to determine the effect of supplementing increased amounts of rumen-protected choline (RPC) from sources with low (L, 28.8%) or high (H, 60.0%) concentration of choline chloride on hepatic metabolism when cows were subjected to feed restriction to develop fatty liver. It was hypothesized that increased supplementation of RPC reduces hepatic triacylglycerol and enhances glycogen concentrations. Pregnant, nonlactating multiparous Holstein cows (n = 110) at mean (± standard deviation) 232 ± 3.9 d of gestation were blocked by body condition (4.01 ± 0.52) and assigned to receive 0 (CON), 12.9 (L12.9 or H12.9), or 25.8 (L25.8 or H25.8) g/d of choline ion. Cows were fed for ad libitum intake on d 1 to 5 and restricted to 50% of the NEL required for maintenance and pregnancy from d 6 to 13. Intake of metabolizable methionine was maintained at 19 g/d during the feed restriction period by supplying rumen-protected methionine. Hepatic tissue was sampled on d 6 and 13 and analyzed for triacylglycerol, glycogen, and mRNA expression of genes involved in choline, glucose, and fatty acids metabolism, cell signaling, inflammation, autophagy, lipid droplet dynamics, lipophagy, and endoplasmic reticulum stress response. Blood was sampled and analyzed for concentrations of fatty acids, ß-hydroxybutyrate (BHB), glucose, triacylglycerol, total cholesterol, and haptoglobin. Orthogonal contrasts evaluated the effect of supplementing RPC [CON vs. (1/4·L12.9 + 1/4·L25.8 + 1/4·H12.9 + 1/4·H25.8)], source of RPC [(1/2·L12.9 + 1/2·L25.8) vs. (1/2·H12.9 + 1/2·H25.8)], amount of RPC [(1/2·L12.9 + 1/2·H12.9) vs. (1/2·L25.8 + 1/2·H25.8)], and interaction between source and amount [(1/2·L12.9 + 1/2·H25.8) vs. (1/2·H12.9 + 1/2·L25.8)]. Least squares means and standard error of the means are presented in sequence as CON, L12.9, L25.8, H12.9, H25.8. Supplementation of RPC reduced hepatic triacylglycerol (9.3 vs. 6.6 vs. 5.1 vs. 6.6 vs. 6.0 ± 0.6% as-is) and increased glycogen contents (1.8 vs. 2.6 vs. 3.6 vs. 3.1 vs. 4.1 ± 0.2% as-is) on d 13 of the experiment. Feeding RPC reduced serum haptoglobin (136.6 vs. 85.6 vs. 80.6 vs. 82.8 vs. 81.2 ± 4.6 µg/mL) during the feed restriction period; however, blood concentrations of fatty acids, BHB, glucose, triacylglycerol, and total cholesterol did not differ among treatments. During feed restriction, supplementation of RPC enhanced the mRNA expression of genes related to choline metabolism (BHMT), uptake of fatty acids (CD36), and autophagy (ATG3), and reduced the expression of a transcript associated with endoplasmic reticulum stress response (ERN1). An increase in the amount of choline ion from 12.9 to 25.8 g/d enhanced the mRNA expression of genes associated with synthesis and assembly of lipoproteins (APOB100), and inflammation (TNFA), whereas it reduced the expression of genes linked to gluconeogenesis (PC), oxidation of fatty acids (ACADM, MMUT), ketogenesis (ACAT1), and synthesis of antioxidants (SOD1) on d 13 of the experiment. Feeding RPC, independent of the product used, promoted lipotropic effects that reduced hepatic lipidosis in dairy cows.

Meta-analysis of the effects of supplemental rumen-protected choline during the transition period on performance and health of parous dairy cows.

The objectives were to use meta-analytic methods to determine the effects of amount of supplemental choline ion as rumen-protected choline (RPC) starting prepartum on production and health of dairy cows. The literature was systematically reviewed and 21 experiments, with up to 66 treatment means and 1,313 prepartum parous cows, were included. All experiments had a treatment with no supplemental choline (0 g/d; n = 30 treatment means), and the amount of choline ion supplemented to treated cows ranged from 5.6 to 25.2 g/d (n = 36 treatment means). Duration of pre- and postpartum feeding of RPC averaged (±standard deviation) 22.0 ± 6.0 and 57.5 ± 42.2 d, respectively. Data collected included the ingredient composition and chemical analyses of pre- and postpartum diets, amount of choline ion supplemented, number of cows per treatment, frequency of health events, and the least squares means and respective standard error of the means for production responses, liver composition, and blood parameters. The concentrations of net energy for lactation and metabolizable amino acids and protein (MP) in pre- and postpartum diets were predicted for each treatment mean using National Research Council (2001). Mixed model meta-analysis was conducted including the random effect of experiment and weighting by the inverse of the standard error of the means squared. Increasing supplementation of choline ion during transition linearly increased pre- (ß = 0.0184 ± 0.00425) and postpartum dry matter intake (ß = 0.0378 ± 0.00974), and yields of milk (ß = 0.436 ± 0.112), energy-corrected milk (ECM; ß = 0.422 ± 0.0992), fat (ß = 0.00555 ± 0.000793), and protein (ß = 0.0138 ± 0.00378). Nevertheless, an interaction between choline and postpartum metabolizable methionine as a percent of MP (METMPPo) was observed for yields of milk, ECM, and protein because as METMPPo increased, the positive response to choline on yields of milk, ECM, and protein decreased. Supplementing choline during transition tended to reduce the risks of retained placenta and mastitis, but it had no effect on metritis, milk fever, displaced abomasum and ketosis, or the concentration of triacylglycerol in the hepatic tissue postpartum. The median amount of choline ion supplemented was 12.9 g/d and responses in postpartum dry matter intake and yields of milk, ECM, fat, and protein to that amount of supplementation were 0.5, 1.6, 1.7, 0.07, and 0.05 kg/d, respectively. No interactions were observed between supplemental choline and prepartum dietary net energy for lactation or metabolizable methionine as a percent of MP. Collectively, feeding RPC during the transition period improves performance in parous cows. Increases in yields of milk and milk components were observed in spite of pre- and postpartum diets, although the increments in milk, ECM, and protein yields with supplementing choline decreased as the concentration of methionine in postpartum diets increased. The optimum dose of choline ion was not detected, but likely it is more than the 12.9 g/d fed in most experiments evaluated in the current meta-analysis. Finally, the meta-analysis identified lack of sufficient data to understand the role of supplemental choline in nulliparous cows.