1832
Hepatic expression of genes associated with glutathione and fatty acid metabolism during the peripartal period reveal beneficial effects of MetaSmart and Smartamine M supplementation on health status in dairy cows
Fifty-seven multiparous Holstein cows were fed a control diet (CON, n = 24; 1.49 Mcal/kg DM prepartum and 1.75 Mcal/kg DM postpartum), CON plus MetaSmart (MS, n = 15; Adisseo France S.A.S.), or CON plus Smartamine M (SM, n = 18; Adisseo France S.A.S.). Treatments began on -21 days in milk (DIM) and continued through 30 DIM. MetaSmart (0.19% of DM) and SM (0.07% of DM) were top-dressed on the CON diet. Liver samples (n = 8-9/treatment) collected at -10, 7, and 21 DIM were used for real-time qPCR of genes associated with metabolism of Met, glutathione, fatty acid, and gluconeogenesis as well as inflammation, oxidative stress, hepatokines, growth hormone signaling, and DNA methylation. Data were analyzed using the MIXED procedure of SAS with the preplanned contrast CON vs. MS+SM. Expression of Met adenosyltransferase 1A (MAT1A) increased (P = 0.001) over time (-10 vs 21 d) in Met-supplemented cows while it decreased (P = 0.002) in CON cows. Glutathione metabolism-related genes such as glutathione reductase (GSR; P = 0.02) and glutathione synthase (GSS; P = 0.004) had lower expression at 21 DIM in Met-supplemented cows, while glutamate-cysteine ligase catalytic tended (GCLC; P = 0.07) to have a similar pattern as GSR and GSS. Expression of 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (HMGCS2) was lower (P = 0.02) in Met-supplemented cows at 21 DIM. HMGCS2 is highly corelated with ketogenesis. Expression of peroxisome proliferator-activated receptor alpha (PPARA; P = 0.04) and phosphoenolpyruvate carboxykinase 1 (PCK1; P = 0.03) was greater in Met-supplemented cows, while a trend (P = 0.06) was observed for the hepatokine fibroblast growth factor 21 (FGF21). Increased expression of MAT1A over time in Met-supplemented cows coupled with greater PPARA expression is suggestive that Met, a methyl donor, might have promoted the activation of PPARA via S-adenosylmethionine by reducing DNA methylation of the PPARA promoter region. The role of the PPARA-FGF21 axis as an activator of gluconeogenesis was underscored by the concomitant upregulation of PCK1 in Met-supplemented cows. Postpartal down-regulation of HMGCS2 in Met-supplemented cows could be related with a lower production of ketones bodies, which agrees with the trend (P = 0.15) observed in the overall group (n = 57) suggesting a lower predisposition to developing ketosis. The parallel down-regulation of GSR, GSS, and GCLCat 21 d might indicate a lower requirement for the antioxidant activity of glutathione in Met-supplemented cows.
Keywords:
Transition cows, gene expression, methionine