Plant-based beverages that attempt to mimic milk are increasingly popular with consumers, but there are profound differences in nutritional composition and microstructure compared to milk. A structural nutrition approach is needed to understand the effect on digestibility of microstructures, bioaccessibility and bioavailability of components, and ultimately on nutritional delivery and human health.
Sustainable dairy development is crucial for global food security, as it converts feed resources into nutrient-dense human food while supporting soil fertility through manure recycling. Milk provides high-quality protein and essential micronutrients, yet rising production demands have intensified challenges related to animal welfare and environmental impacts. Addressing these issues requires integrated strategies, including precision monitoring technologies, enteric methane inhibitors, and improved manure management. A balanced approach aligning productivity with animal health and ecological integrity is essential for future dairy systems.
Dairy cattle's lactation efficiency has increased over the last decades, which is mainly attributed to high milk production and elevated nutrient requirements, especially protein and amino acids (AA) requirements. The transition period is considered one of the most crucial periods of a dairy cow's life, with the largest number of health disorders happening within the first 14 days in milk. Changes in dairy cow metabolic conditions might have had a severe impact on dairy cow health, fertility, and production, particularly milk and milk component yields. One of the applied strategies to prevent these negative impacts is balancing amino acids profile in dairy cattle feeds, primarily, rumen bypass methionine and lysine (RPM and RPL) to meet the requirements through increasing the metabolizable amino acid (AA) for intestinal absorption. NASEM (2021) presented a novel concept based on considering 5 indispensable amino acid (IAA) rather than the more aggregated metabolizable protein (MP) and the Lys–Met ratio. Continued attempts to improve the understanding of AA pathways make the possibility of new strategies to minimize the negative impacts on dairy cow metabolic status changes. Previous research observed beneficial impacts of supplementing RPM and RPL in transition dairy cow diets either/both (pre-and postpartum periods) on dry matter intake, milk performance, plasma AA concentration, the occurrence rate of metabolic disorders, and immune response; however, the findings were inconsistent. Therefore, this review focused on the inconsistencies in the data and sought research gaps in this area.
Circulating concentrations of nonesterified fatty acids (NEFAs) are elevated due to lipid mobilization from adipose tissue in periparturient dairy cows. Although this metabolic adaptation facilitates energy homeostasis under the negative energy balance condition, sustained systemic NEFA overload induces profound hepatic impairment. Emerging evidence identifies excessive NEFAs to be the pathophysiological cornerstone of periparturient disorders; however, the precise molecular mechanisms underlying NEFA-induced hepatotoxicity remain incompletely characterized, hindering the development of effective preventive and therapeutic strategies. This literature review synthesizes contemporary insights into key cellular pathways implicated in NEFA-mediated hepatotoxicity: disorders in lipid and carbohydrate metabolism, impairment of autophagy, excessive inflammatory response, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress, and finally, cell death. Critical analysis reveals two underexplored dimensions in current research paradigms: (1) The dynamic composition of circulating NEFAs modulates hepatotoxic potency through differential membrane incorporation and signaling pathway activation, suggesting that improving blood NEFA composition through dietary fat supplementation offers a potential strategy; and (2) the periparturient inflammatory milieu potentiates NEFA toxicity, suggesting targeted anti-inflammatory interventions ameliorate transition period adaptation. Consequently, this review advances our mechanistic understanding while providing translational frameworks for improving periparturient management through precision nutrition and therapeutic development.
Limited land or water resources, climate variability, and price fluctuations challenge the consistent availability of alfalfa forage. Barley forage, with high energy and low agronomic costs, shows promise as an alternative in dairy diets. Our objective was to examine the effects of replacing alfalfa hay with whole-plant barley silage on behavioral patterns, ruminal fermentation, nutrient digestibility, and lactation productivity. A 3 × 3 Latin square design was employed, involving 12 multiparous Holstein cows (days in milk = 122 ± 6; milk production = 49.3 ± 2.0 kg; mean ± standard deviation). Alfalfa hay was partially or completely substituted with barley silage as (1) a control diet without barley silage (BS0; 23.2% corn silage + 15.6% alfalfa hay), (2) 23.2% corn silage + 7.8% alfalfa hay + 7.9% barley silage (BS50), and (3) 23.2% corn silage + 15.7% barley silage + 0% alfalfa hay (BS100). Dry matter intake was the greatest in BS50-fed cows (27.3 kg/day) and lowest with BS100-fed cows (24.4 kg/day). Time spent eating, ruminating, and chewing was not different across treatments. BS50-fed cows had the highest propionate concentration and the lowest acetate and valerate concentrations. Cows fed BS50 and BS100 had lower starch digestibility than BS0. Milk production was not different between diets, but feed efficiency was the greatest with BS100-fed cows, resulting in the highest income over feed cost estimated in this group. Overall, barley silage can replace alfalfa hay in high-concentrate diets fed to mid-lactation cows, as its total replacement improved the efficiency of feed conversion into milk.
Perinatal cows are often in a state of negative energy balance (NEB), and hepatic gluconeogenesis is an important energy source in ruminants. NEB can lead to metabolic disorders such as ketosis. β-Hydroxybutyrate (BHB) is a major ketone body that acts as an energy substrate; however, its role and mechanism in hepatic gluconeogenesis in perinatal cows are unclear. The aim of this study was to investigate the compensatory effects of BHB in hepatic gluconeogenesis in dairy cows, particularly its effect on fructose 1,6-bisphosphatase 1 (FBP1) and phosphoenolpyruvate carboxykinase 1 (PCK1), which are key rate-limiting enzymes in gluconeogenesis. We performed Kbhb proteomic analysis of liver tissue samples from perinatal cows and found a significant enrichment of the gluconeogenic pathway. When bovine hepatocytes were treated with different concentrations of BHB, there was a significant increase in cellular glucose production and FBP1/PCK1 activity. With regard to the underlying mechanisms, the findings implied that Kbhb of FBP1/PCK1 may occur in a BHB concentration- and time-dependent manner. Furthermore, Kbhb of FBP1/PCK1 was found to be regulated by histone acetyltransferase p300 (p300) and histone deacetylase (HDACs). Mass spectrometry analysis revealed that Kbhb occurred at lysine (K) 43 of FBP1 and K191 of PCK1. In conclusion, our results demonstrate that the compensatory effects of BHB induced an increase in the enzymatic activity of FBP1 and PCK1 through Kbhb modification at the K43 site of FBP1 and the K191 site of PCK1; in turn, it enhances the hepatic gluconeogenesis of cows to certain BHB concentrations.
The physiological adaptation responses of peripartum cows to negative energy balance, including fat mobilization and insulin resistance, are controlled by hormones. Excessive growth hormone (GH) promotes fat mass loss and insulin resistance in nonruminants. Despite elevated circulating GH in postpartum cows, its regulatory mechanisms on lipid metabolism and insulin signaling pathways in bovine adipocytes remain unresolved. This research study intends to examine the effects that GH has on lipolysis and insulin sensitivity within bovine adipocytes and provide mechanistic insights. We discovered that GH stimulates lipolysis and compromised insulin sensitivity, as evidenced by elevated glycerol release, reduced triglyceride accumulation, and diminished lipid droplet formation, along with impaired insulin-mediated phosphorylation of protein kinase B (AKT) in GH-treated adipocytes. The combination of GH and isoproterenol exacerbated the insulin insensitivity and lipolysis induced by GH. Phosphorylation levels of ERK and HSL were elevated in adipocytes treated with GH, suggesting that GH activated the ERK/HSL signaling pathway. The mRNA abundance of cell death-inducing DNA fragmentation factor-α-like effector c and perilipin 1 was downregulated by GH in adipocytes. Importantly, inhibiting ERK and HSL (hormone sensitive lipase; encoded by LIPE) attenuated GH-induced lipolysis and insulin insensitivity. Collectively, GH enhances lipolysis and impairs insulin sensitivity in bovine adipocytes via activating the ERK/HSL signaling pathway at least partially. Therefore, inhibiting the ERK/HSL signaling pathway may be a promising means to avoid excessive fat mobilization and insulin resistance in dairy cows during the peripartum period.
High-yielding dairy cows are susceptible to mammary gland oxidative stress due to prolonged intensive lactation, leading to redox imbalance. Our previous research linked this condition to reduced lactation lifespan. This study compared mammary glands from high-yielding and normal-yielding cows, revealing significant oxidative stress in high-yielders, evidenced by decreased FRAP and SOD levels, and increased GSH, MDA, and H2O2. Mitochondrial function was disrupted, with impaired dynamics. Metabolomic analysis identified a significant downregulation of Myo-inositol (MI) in high-yielding cows. Using H2O2-stimulated bovine mammary epithelial cells (MAC-T) as an in vitro oxidative stress model, we confirmed MI depletion, mitochondrial fission, cellular senescence, and decreased Sirt5 protein. MI supplementation upregulated mitochondrial fusion proteins (OPA1, MFN1, and MFN2) and downregulated fission proteins (FIS1 and Drp1), alleviating oxidative stress. Mechanistic studies revealed that Sirt5 knockdown reduced Nrf2 expression, and inhibiting Nrf2 with retinoic acid (RA) abolished MI's protective effects. This demonstrates that MI alleviates oxidative stress in MAC-T cells primarily by activating the Sirt5/Nrf2 pathway to promote mitochondrial fusion. These findings elucidate a novel mechanism for MI's antioxidant role in the dairy cow mammary gland.