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      Effect of weaning strategies on biosynthesis of oxylipids in Holstein dairy calves

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          Graphical Abstract

          Summary: Oxylipids are synthesized from the oxidation of certain polyunsaturated fatty acids by enzymatic or nonenzymatic pathways and are responsible for promoting or resolving inflammation. Their roles are related to the fatty acid source and pathways from which they are derived. However, no evidence in the current literature explains how weaning stress in dairy calves affects the biosynthesis and prevalence of oxylipids. This study aimed to bridge that gap and found that weaning pace can affect the plasma concentration of oxylipids.

          Highlights

          • Seventy-one Holstein dairy calves were weaned early or late and abruptly or gradually.

          • Abrupt weaning increased anti-inflammatory oxylipid 17,18-DiHETE.

          • Linoleic acid-derived proinflammatory oxylipids predominated with gradual weaning.

          • Oxylipids are affected by the pace of weaning, regardless of age.

          Abstract

          The aim of this study was to determine the effect of the weaning calves at 2 ages (early vs. late) and 2 weaning paces (abrupt over 3 d vs. gradual over 14 d) on plasma oxylipids. Seventy-one dairy calves (38.8 ± 4.4 kg, BW ± SD), blocked by sex and BW at birth, were randomly assigned in a 2 × 2 factorial arrangement of treatments. The factors were weaning age (early: 6–7 wk vs. late: 8–9 wk) and weaning pace (abrupt: 3 weaning steps over 2 d vs. gradual: 7 weaning steps over 14 d), generating 4 treatment groups: early-abrupt, early-gradual, late-abrupt, and late-gradual. Blood samples were collected from the jugular vein 1 d preweaning, and one day postweaning. Oxylipids concentration was measured by liquid chromatography-tandem MS. Fatty acid profile (including nonesterified fatty acids) was also assessed. Weaning pace, age, pace × age, BW at birth, and sex were included as fixed effect and cohort was included as random effect in the model. Linoleic acid derivatives 13- oxooctadecadienoic (OxoODE) and 9-OxoODE had a greater concentration in calves abruptly weaned when compared with those for gradually weaned calves. Calves weaned gradually showed a greater concentration of 9-hydroxyoctadecadienoic (HODE), 13-HODE, 12,13-dihydroxyoctadecenoic (DiHOME), 9,10-DiHOME, all linoleic acid-derived compared with that for abruptly weaned calves. Anti-inflammatory oxylipid 17,18-dihydroxyeicosatrienoic, an eicosapentaenoic acid derivative, was greater in calves abruptly weaned compared with those gradually weaned. Overall, the pace of weaning affected the plasma concentration of oxylipids, demonstrating that weaning pace affects the oxylipids status involved in inflammation in dairy calves.

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          Most cited references23

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          Elevated non-esterified fatty acids and β-hydroxybutyrate and their association with transition dairy cow performance.

          Dairy cows pass through a period of negative energy balance as they transition from late gestation to early lactation. Poor adaptation through this period, expressed as excessively elevated concentrations of non-esterified fatty acids (NEFAs) pre- or post-partum and elevated concentrations of β-hydroxybutyrate post-partum, increases an individual animal's risk of post-partum disease, removal from the herd, reproductive difficulty, and reduced milk production. Field studies have shown that subclinical ketosis often affects 40% of cows in a herd although the incidence can be as high as 80%. Peak incidence occurs at 5 days in milk, and cows that develop subclinical ketosis in the first week of lactation have a higher risk of negative effects and reduced milk production than cows that develop subclinical ketosis in the second week of lactation. Herds with more than a 15-20% prevalence of excessively elevated concentrations of NEFAs and β-hydroxybutyrate in early lactation have higher rates of negative subsequent events, poorer reproduction, and lower milk yield than herds with a lower prevalence of negative energy balance. This paper reviews (1) strategies for testing of energy-related metabolites, (2) consequences of poor adaptation to negative energy balance (for individual animals and for herds), (3) treatment approaches for affected cows, and (4) economic considerations for testing and treating cows with poor adaptation to negative energy balance.
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            Bioactivation of leukotoxins to their toxic diols by epoxide hydrolase

            Leukotoxin is a linoleic acic oxide produced by leukocytes and has been associated with the multiple organ failure and adult respiratory distress syndrome seen in some severe burn patients. Leukotoxin has been reported to be toxic when injected into animals intravenously. Herein, we report that this lipid is not directly cytotoxic in at least two in vitro systems. Using a baculovirus expression system we demonstrate that leukotoxin is only cytotoxic in the presence of epoxide hydrolases. In addition, it is the diol metabolite that proves toxic to pulmonary alveolar epithelial cells, suggesting a critical role for the diol in leukotoxin-associated respiratory disease. In vivo data also support the toxicity of leukotoxin diol. For the first time we demonstrate that soluble epoxide hydrolase can bioactivate epoxides to diols that are apparently cytotoxic. Thus leukotoxin should be regarded as a protoxin corresponding to the more toxic diol. This clearly has implications for designing new clinical interventions.
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              Adipogenic role of alternatively activated macrophages in β-adrenergic remodeling of white adipose tissue.

              De novo brown adipogenesis involves the proliferation and differentiation of progenitors, yet the mechanisms that guide these events in vivo are poorly understood. We previously demonstrated that treatment with a β3-adrenergic receptor (ADRB3) agonist triggers brown/beige adipogenesis in gonadal white adipose tissue following adipocyte death and clearance by tissue macrophages. The close physical relationship between adipocyte progenitors and tissue macrophages suggested that the macrophages that clear dying adipocytes might generate proadipogenic factors. Flow cytometric analysis of macrophages from mice treated with CL 316,243 identified a subpopulation that contained elevated lipid and expressed CD44. Lipidomic analysis of fluorescence-activated cell sorting-isolated macrophages demonstrated that CD44+ macrophages contained four- to five-fold higher levels of the endogenous peroxisome-proliferator activated receptor gamma (PPARγ) ligands 9-hydroxyoctadecadienoic acid (HODE), and 13-HODE compared with CD44- macrophages. Gene expression profiling and immunohistochemistry demonstrated that ADRB3 agonist treatment upregulated expression of ALOX15, the lipoxygenase responsible for generating 9-HODE and 13-HODE. Using an in vitro model of adipocyte efferocytosis, we found that IL-4-primed tissue macrophages accumulated lipid from dying fat cells and upregulated expression of Alox15. Furthermore, treatment of differentiating adipocytes with 9-HODE and 13-HODE potentiated brown/beige adipogenesis. Collectively, these data indicate that noninflammatory removal of adipocyte remnants and coordinated generation of PPARγ ligands by M2 macrophages provides localized adipogenic signals to support de novo brown/beige adipogenesis.
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                Author and article information

                Contributors
                Journal
                JDS Commun
                JDS Commun
                JDS Communications
                Elsevier
                2666-9102
                18 September 2024
                January 2025
                18 September 2024
                : 6
                : 1
                : 149-153
                Affiliations
                [1 ]Department of Animal, Veterinary and Food Sciences, University of Idaho, Moscow, ID 83844
                [2 ]Department of Large Animal Clinical Science, Michigan State University, East Lansing, MI 48824
                [3 ]Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada T6G 2P5
                Author notes
                Article
                S2666-9102(24)00144-3
                10.3168/jdsc.2024-0600
                11770287
                39877181
                9734a401-1d96-47c5-83e3-2e01852dee8f
                © 2024.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 April 2024
                : 30 August 2024
                Categories
                Short Communication
                Short Communication

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