In this study, we explored mechanisms related to glucose and fatty acid metabolism in Holstein–Friesian multiparous dairy cows during lactation under two feeding strategies. From 0 to 180 days postpartum, cows were fed total mixed ration (TMR) ad libitum (non-grazing group, G0) or grazed Festuca arundinacea or Medicago sativa and were supplemented with 5.4 kg DM/d of an energy-protein concentrate (grazing group, G1). From 180 to 250 days postpartum, all cows grazed F. arundinacea and were supplemented with TMR. Plasma samples and liver biopsies were collected at −14, 35, 60, 110, 180, and 250 days in milk (DIM) for metabolite, hormone, gene expression, and western blot analysis. Our results showed increased levels of negative energy balance markers: plasma non-esterified fatty acids (NEFA), liver triglyceride and plasma β-hydroxybutyrate (BHB) (P < 0.01), triglyceride and β-hydroxybutyrate concentration were especially elevated for G1 cows. Also, hepatic mRNA expression of gluconeogenic enzymes was upregulated during early lactation (P < 0.05). In particular, methymalonyl-CoA mutase expression was increased for G0 cows (P < 0.05) while pyruvate carboxylase (PC) expression was increased for G1 cows (P < 0.05), suggesting differential gluconeogenic precursors for different feeding strategies. Phosphorylation of AMP-activated protein kinase was increased in early lactation vs. late lactation (P < 0.01) and negatively correlated with PC mRNA levels. The positive association of gluconeogenic genes with proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) hepatic expression supported the importance of this transcription factor in glucose metabolism. The peroxisome proliferator-activated receptor alpha (PPARA) mRNA was increased during early lactation (P < 0.05), and was positively associated to PPARGC1A, carnitine palmitoyl-transferase 1, and hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) mRNA expression. Alongside, hepatic mRNA expression of FABP was decreased for G1 vs. G0 cows (P < 0.05), possibly linked to impaired fatty acid transport and related to accumulation of liver triglycerides, evidencing G1 cows fail to adapt to the demands of early lactation. In sum, our results showed that metabolic adaptations related to early lactation negative energy balance can be affected by feeding strategy and might be regulated by the metabolic sensors AMPK, SIRT1, and coordinated by transcription factors PPARGC1A and PPARA.

The objective of this study was to assess hepatic ATP synthesis in Holstein cows of North American and New Zealand origins and the gluconeogenic pathway, one of the pathways with the highest ATP demands in the ruminant liver. Autumn-calving Holstein cows of New Zealand and North American origins were managed in a pasture-based system with supplementation of concentrate that represented approximately 33% of the predicted dry matter intake during 2017, 2018, and 2019, and hepatic biopsies were taken during mid-lactation at 174 ± 23 days in milk. Cows of both strains produced similar levels of solids-corrected milk, and no differences in body condition score were found. Plasma glucose concentrations were higher for cows of New Zealand versus North American origin. Hepatic mitochondrial function evaluated measuring oxygen consumption rates showed that mitochondrial parameters related to ATP synthesis and maximum respiratory rate were increased for cows of New Zealand compared with North American origin. However, hepatic gene expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and pyruvate dehydrogenase kinase was increased in North American compared with New Zealand cows. These results altogether suggest an increased activity of the tricarboxylic cycle in New Zealand cows, leading to increased ATP synthesis, whereas North American cows pull tricarboxylic cycle intermediates toward gluconeogenesis. The fact that this occurs during mid-lactation could account for the increased persistency of North American cows, especially in a pasture-based system. In addition, we observed an augmented mitochondrial density in New Zealand cows, which could be related to feed efficiency mechanisms. In sum, our results contribute to the elucidation of hepatic molecular mechanisms in dairy cows in production systems with higher inclusion of pastures.

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