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  1. Article ; Online: Inflammatory tone in liver and adipose tissue in dairy cows experiencing a healthy transition from late pregnancy to early lactation.

    McGuckin, M M / Giesy, S L / Overton, T R / Boisclair, Y R

    Journal of dairy science

    2023  Volume 106, Issue 11, Page(s) 8122–8132

    Abstract: The transition from late pregnancy (LP) to early lactation (EL) in dairy cows is characterized by a major reorganization of the metabolic activities of liver and adipose tissue in support of milk synthesis. This reorganization has been attributed in ... ...

    Abstract The transition from late pregnancy (LP) to early lactation (EL) in dairy cows is characterized by a major reorganization of the metabolic activities of liver and adipose tissue in support of milk synthesis. This reorganization has been attributed in large part to variation in the plasma concentration and actions of growth hormone, insulin, and other metabolic hormones. A role for the immune system has also been suggested by a near-universal rise in circulating levels of liver-derived acute-phase proteins (APP) in early lactating cows. However, less attention has been devoted to the possibility that resident macrophages of liver and adipose tissue adopt a proinflammatory state (referred herein as inflammatory tone) in parallel with the rise in plasma APP. We addressed this question by measuring the expression of genes expressed predominantly in the resident macrophage population of liver and adipose tissue and indicative of a proinflammatory (tumor necrosis factor α, IL-6, IL-12, resistin, and cluster of differentiation 80 [CD80]) or anti-inflammatory state (IL-10 and chitinase-3-like protein 1 [CHI3L1]). In a first group of cows, none of these inflammatory gene markers were regulated in liver between LP on d -29 (relative to parturition) and on d 8 of EL despite 1.7 to 5.6-fold upregulation in the expression of the APP (haptoglobin, serum amyloid α, and orosomucoid 1). In a second group of healthy cows, expression of the inflammatory gene markers did not differ between livers with low (<5.3%) or high (>11.5%) triglyceride content on d 7 of EL. In adipose tissue, a modest increase in inflammatory tone was suggested between LP and EL by increased CD80 expression and decreased CHI3L1 expression in EL. To assess the possibility that inflammatory tone would be more prominent if assayed in a cell compartment enriched with macrophages, adipose tissue was obtained in LP on d -28 and in EL on d +10 from cows experiencing a healthy transition period and fractionated into its adipocyte and stromal vascular cell (SVC) compartments. Expression of inflammatory gene markers was higher in SVC than adipocytes but remained unregulated in SVC between LP and EL. Overall, these results suggest little change in the inflammatory tone of resident macrophages in liver and adipose tissue of healthy transition dairy cows and do not support a role for the local immune system in the reorganization of metabolism in these tissues at the onset of lactation.
    MeSH term(s) Female ; Pregnancy ; Cattle ; Animals ; Lactation/physiology ; Adipose Tissue/metabolism ; Parturition ; Milk/metabolism ; Liver/metabolism ; Postpartum Period
    Language English
    Publishing date 2023-08-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 242499-x
    ISSN 1525-3198 ; 0022-0302
    ISSN (online) 1525-3198
    ISSN 0022-0302
    DOI 10.3168/jds.2023-23373
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Time-dependent effect of trans-10,cis-12 conjugated linoleic acid on gene expression of lipogenic enzymes and regulators in mammary tissue of dairy cows.

    Harvatine, Kevin J / Boisclair, Y R / Bauman, Dale E

    Journal of dairy science

    2018  Volume 101, Issue 8, Page(s) 7585–7592

    Abstract: Trans-10,cis-12 conjugated linoleic acid (CLA) has been identified as an intermediate of rumen fatty acid biohydrogenation that caused milk fat depression (MFD) in the dairy cow. Previous studies in cows experiencing CLA- and diet-induced MFD have ... ...

    Abstract Trans-10,cis-12 conjugated linoleic acid (CLA) has been identified as an intermediate of rumen fatty acid biohydrogenation that caused milk fat depression (MFD) in the dairy cow. Previous studies in cows experiencing CLA- and diet-induced MFD have identified reduced mammary expression of the master lipogenic regulator sterol response element transcription factor 1 (SREBF1) and many of its dependent genes. To distinguish between primary mechanisms regulating milk fat synthesis and secondary adaptations to the reduction in milk fat, we conducted a time-course experiment. Eleven dairy cows received by abomasal infusion an initial priming dose of 6.25 g of CLA followed by 12.5 g/d delivered in multiple pulses per day for 5 d. Cows were milked 3×/d and mammary biopsies were obtained under basal condition (prebolus control) and 12, 30, and 120 h relative to initiation of CLA infusion. Milk fat concentration and yield decreased progressively reaching a nadir at 69 h (1.82% and 38.2 g/h) and averaged 2.03 ± 0.19% and 42.1 ± 4.10 g/h on the last day of treatment (±standard deviation). Expression of fatty acid synthase (FASN) and lipoprotein lipase (LPL) were decreased at 30 and 120 h compared with control. Expression of SREBF1 and THRSP were also decreased at 30 and 120 h compared with control. Additionally, we failed to observe changes in other factors, including peroxisome proliferator-activated receptor γ and liver × receptor β and milk fat globular membrane proteins, during CLA treatment. However, expression of milk fat globular membrane proteins were decreased after 14 d of diet-induced MFD in samples from a previous experiment, indicating a possible long-term response. The rapid decrease in lipogenic enzymes, SREBF1, and THRSP provide strong support for their transcriptional regulation as a primary mechanism of milk fat depression.
    MeSH term(s) Adipose Tissue/metabolism ; Animals ; Cattle/metabolism ; Diet ; Fatty Acid Synthases/genetics ; Fatty Acids ; Female ; Lactation ; Linoleic Acids, Conjugated/administration & dosage ; Lipogenesis/genetics ; Lipogenesis/physiology ; Lipoprotein Lipase/genetics ; Mammary Glands, Animal/metabolism ; Milk
    Chemical Substances Fatty Acids ; Linoleic Acids, Conjugated ; Fatty Acid Synthases (EC 2.3.1.85) ; Lipoprotein Lipase (EC 3.1.1.34)
    Language English
    Publishing date 2018-05-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 242499-x
    ISSN 1525-3198 ; 0022-0302
    ISSN (online) 1525-3198
    ISSN 0022-0302
    DOI 10.3168/jds.2017-13935
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Effects of recombinant bovine interleukin-8 (rbIL-8) treatment on health, metabolism, and lactation performance in Holstein cattle III: Administration of rbIL-8 induces insulin resistance in bull calves.

    Zinicola, M / Menta, P R / Ribeiro, B L / Boisclair, Y / Bicalho, R C

    Journal of dairy science

    2019  Volume 102, Issue 11, Page(s) 10329–10339

    Abstract: Our previous work has suggested that recombinant bovine interleukin-8 (rbIL-8) treatment might influence cow metabolism. Therefore, this study was conducted to initially assess the effects of systemic administration of rbIL-8 on response to a glucose ... ...

    Abstract Our previous work has suggested that recombinant bovine interleukin-8 (rbIL-8) treatment might influence cow metabolism. Therefore, this study was conducted to initially assess the effects of systemic administration of rbIL-8 on response to a glucose challenge, blood metabolites, insulin, growth hormone, insulin-like growth factor-1, immune cell populations, and inflammatory parameters in Holstein bull calves. Calves from 30 ± 6 d of life were individually housed and randomly allocated to 1 of 2 treatment groups: rbIL-8 (rbIL-8, n = 10) and control (CTR, n = 8). Calves assigned to the rbIL-8 group received 1 s.c. injection (d 1, 0900 h) and 6 i.v. injections (d 1 at 1600 h, d 2 and 3 at 0900 h and 1600 h, and d 4 at 0900 h) of rbIL-8 (4 μg/kg of body weight), whereas the CTR group received 2 mL of sterile saline solution at each time point. Day of enrollment was considered as d 1, and the study duration was 10 d. Insulin concentrations and whole-body glucose disappearance were evaluated by an i.v. glucose tolerance test conducted at 12 h and 7 d following the last rbIL-8 injection. Rectal temperature and blood samples were collected on d 1, 2, 3, and 4 at -30 (before treatment, 0830 h), 30, 60, 120, 240, and 360 min relative to treatment, and daily at 0830 h for the rest of the study period. Serum was harvested, and the following parameters were measured: β-hydroxybutyrate (BHB), nonesterified fatty acids, glucose, insulin, plasma urea nitrogen, haptoglobin, and differential blood count. Significant differences were considered when P ≤ 0.05 and a trend if 0.05

    MeSH term(s) 3-Hydroxybutyric Acid/blood ; Animals ; Area Under Curve ; Blood Glucose/analysis ; Blood Glucose/drug effects ; Blood Glucose/metabolism ; Blood Urea Nitrogen ; Body Temperature ; Body Weight ; Cattle ; Fatty Acids, Nonesterified/blood ; Glucose Tolerance Test ; Haptoglobins/analysis ; Insulin/blood ; Insulin Resistance ; Insulin-Like Growth Factor I ; Interleukin-8/administration & dosage ; Interleukin-8/adverse effects ; Interleukin-8/pharmacology ; Leukocyte Count/veterinary ; Male ; Recombinant Proteins/administration & dosage ; Recombinant Proteins/adverse effects ; Recombinant Proteins/pharmacology
    Chemical Substances Blood Glucose ; Fatty Acids, Nonesterified ; Haptoglobins ; IGF1 protein, human ; Insulin ; Interleukin-8 ; Recombinant Proteins ; Insulin-Like Growth Factor I (67763-96-6) ; 3-Hydroxybutyric Acid (TZP1275679)
    Language English
    Publishing date 2019-09-05
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial, Veterinary
    ZDB-ID 242499-x
    ISSN 1525-3198 ; 0022-0302
    ISSN (online) 1525-3198
    ISSN 0022-0302
    DOI 10.3168/jds.2019-16336
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Variation in x-box binding protein 1 (XBP1) expression and its dependent endoplasmic reticulum chaperones does not regulate adiponectin secretion in dairy cows.

    Krumm, C S / Giesy, S L / Orndorff, C L / Boisclair, Y R

    Journal of dairy science

    2018  Volume 101, Issue 6, Page(s) 5559–5570

    Abstract: Adiponectin is an insulin-sensitizing hormone produced predominantly by adipose tissue; it circulates as oligomers of 3, 6, 18, or more units. Plasma adiponectin might be involved in the development of insulin resistance in transition dairy cows because ... ...

    Abstract Adiponectin is an insulin-sensitizing hormone produced predominantly by adipose tissue; it circulates as oligomers of 3, 6, 18, or more units. Plasma adiponectin might be involved in the development of insulin resistance in transition dairy cows because it falls to a nadir around parturition. The possibility that this regulation occurs through a post-transcriptional mechanism was suggested in a previous study that showed unchanged adiponectin mRNA abundance combined with reduced expression of endoplasmic reticulum (ER) chaperones implicated in assembly of adiponectin oligomers. Expression of ER chaperones is controlled by x-box binding protein 1 (XBP1) and activating transcription factor 6 (ATF6), suggesting a model whereby transcriptional regulation of ER chaperones during the transition period contributes to the regulation of adiponectin production. In support of this model, XBP1 expression in adipose tissue, measured either as the active spliced XBP1 mRNA or as the total of all XBP1 mRNA isoforms, was 45% lower on d 8 of lactation than 4 wk before parturition; ATF6 mRNA abundance remained unchanged over the same period. To assess the functional importance of XBP1, preadipocytes isolated from pregnant cows were differentiated into adipocytes that secrete adiponectin. Infection of differentiating cells with an adenovirus expressing the active spliced version of bovine XBP1 did not alter adiponectin mRNA but increased the expression of ER chaperones 1.5- to 5-fold. Despite the latter, XBP1 overexpression did not affect the total amount of adiponectin secreted in medium. In additional experiments, adiponectin production was dependent on exogenous lipid in the medium and was reduced during incubation with tumor necrosis factor-α (TNFα). Accordingly, we asked whether the repressive effects of these factors on adiponectin production were related to a reduction in the expression of adiponectin or determinants of ER function (XBP1, ATF6, and ER chaperones). Exogenous lipid had no effect on the expression of any of these genes, whereas TNFα repressed adiponectin mRNA abundance by 61% but had little effect on determinants of ER function. Overall, this work shows that XBP1 is a positive regulator of ER chaperone expression in adipose tissue but provides no support for XBP1 and its dependent ER chaperones in the regulation of adiponectin production in bovine adipocytes. Mechanisms accounting for reduced plasma adiponectin in transition cows remain poorly understood.
    MeSH term(s) Activating Transcription Factor 6 ; Adiponectin/metabolism ; Animals ; Cattle/metabolism ; DNA-Binding Proteins/physiology ; Endoplasmic Reticulum/metabolism ; Female ; Gene Expression Regulation ; Molecular Chaperones/chemistry ; Pregnancy ; Regulatory Factor X Transcription Factors ; Transcription Factors/physiology ; X-Box Binding Protein 1/metabolism
    Chemical Substances Activating Transcription Factor 6 ; Adiponectin ; DNA-Binding Proteins ; Molecular Chaperones ; Regulatory Factor X Transcription Factors ; Transcription Factors ; X-Box Binding Protein 1
    Language English
    Publishing date 2018-03-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 242499-x
    ISSN 1525-3198 ; 0022-0302
    ISSN (online) 1525-3198
    ISSN 0022-0302
    DOI 10.3168/jds.2017-14048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. II. Pharmacokinetics, whole-animal performance, and lipid metabolism.

    Caixeta, L S / Giesy, S L / Krumm, C S / Perfield, J W / Butterfield, A / Boisclair, Y R

    Journal of dairy science

    2019  Volume 102, Issue 12, Page(s) 11597–11608

    Abstract: Dairy cows cope with severe energy insufficiency in early lactation by engaging in intense and sustained mobilization of fatty acids from adipose tissue. An unwanted side effect of this adaptation is excessive lipid accumulation in the liver, which in ... ...

    Abstract Dairy cows cope with severe energy insufficiency in early lactation by engaging in intense and sustained mobilization of fatty acids from adipose tissue. An unwanted side effect of this adaptation is excessive lipid accumulation in the liver, which in turn impairs hepatic functions. Mice experiencing increased hepatic fatty acid flux are protected from this condition through coordinated actions of the newly described hormone fibroblast growth factor-21 (FGF21) on liver and adipose tissue. The possibility of an analogous role for FGF21 in dairy cows is suggested by its rapid increase in plasma levels around parturition followed by chronically elevated levels in the first few weeks of lactation. To test this hypothesis, dairy cows were randomly assigned on d 12.6 ± 2.2 (± standard error) of lactation to receive either an excipient (control; n = 6) or recombinant human FGF21 (n = 7), first as an FGF21 bolus of 3 mg/kg of body weight (BW) followed 2 d later by a constant i.v. infusion of FGF21 at a rate of 6.3 mg/kg of metabolic BW for 9 consecutive days. After bolus administration, human FGF21 circulated with a half-life of 194 min, and its constant infusion increased total plasma concentration 117-fold over levels in excipient-infused cows. The FGF21 treatment had no effect on voluntary feed intake, milk yield, milk energy output, or net energy balance measured over the 9-d infusion or on final BW. Plasma fatty acids circulated at lower concentrations in the FGF21 group than in the control group for the 8-h period following bolus administration, but this reduction was not significant during the period of constant i.v. infusion. Treatment with FGF21 caused a 50% reduction in triglyceride content in liver biopsies taken at the end of the constant i.v. infusion without altering the mRNA abundance of key genes involved in the transport, acyl coenzyme A activation, or oxidation of fatty acids. In contrast, FGF21 treatment ablated the recovery of plasma insulin-like growth factor-1 seen in control cows during the 9-d i.v. infusion period despite a tendency for higher plasma growth hormone. This effect was associated with increased hepatic mRNA abundance of the intracellular inhibitor of growth hormone receptor trafficking, LEPROT. Overall, these data confirm the ability of FGF21 to reduce lipid accumulation in bovine liver and suggest the possibility that FGF21 does so by attenuating the hepatic influx of adipose tissue-derived fatty acids.
    MeSH term(s) Adipose Tissue/metabolism ; Animals ; Cattle/physiology ; Energy Metabolism/drug effects ; Fatty Acids/metabolism ; Female ; Fibroblast Growth Factors/administration & dosage ; Fibroblast Growth Factors/genetics ; Fibroblast Growth Factors/pharmacokinetics ; Growth Hormone/blood ; Humans ; Lactation ; Lipid Metabolism/drug effects ; Liver/metabolism ; Mice ; Milk/metabolism ; Parturition ; RNA, Messenger/genetics ; Random Allocation ; Receptors, Somatotropin/metabolism ; Recombinant Proteins ; Triglycerides/metabolism
    Chemical Substances Fatty Acids ; RNA, Messenger ; Receptors, Somatotropin ; Recombinant Proteins ; Triglycerides ; fibroblast growth factor 21 ; Fibroblast Growth Factors (62031-54-3) ; Growth Hormone (9002-72-6)
    Language English
    Publishing date 2019-09-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 242499-x
    ISSN 1525-3198 ; 0022-0302
    ISSN (online) 1525-3198
    ISSN 0022-0302
    DOI 10.3168/jds.2019-16696
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. I. Effects on signaling and indices of insulin action.

    Krumm, C S / Giesy, S L / Caixeta, L S / Perfield, J W / Sauerwein, H / Moore, B L / Boisclair, Y R

    Journal of dairy science

    2019  Volume 102, Issue 12, Page(s) 11586–11596

    Abstract: Modern dairy cows rely on hormonally driven mechanisms to coordinate the metabolic adaptations needed to meet the energy and nutrient deficits of early lactation. In the case of glucose, dairy cows cope with its scarcity during early lactation via ... ...

    Abstract Modern dairy cows rely on hormonally driven mechanisms to coordinate the metabolic adaptations needed to meet the energy and nutrient deficits of early lactation. In the case of glucose, dairy cows cope with its scarcity during early lactation via reduced plasma concentrations of insulin and the insulin sensitizing hormone adiponectin and increased insulin resistance. Reduced insulin action promotes diversion of available glucose to the mammary gland but increases susceptibility to diseases if excessive. In earlier work, we reported that the insulin sensitizing hormone fibroblast growth factor-21 (FGF21) is increased in periparturient dairy cows and identified liver and adipose tissue as possible targets. These observations raised the possibility that FGF21 acts directly on these tissues to limit the insulin resistance of early lactation. To test this hypothesis, dairy cows were randomly assigned on d 12.6 ± 2.2 (± standard error) of lactation to receive either excipient (n = 6) or recombinant human FGF21 (n = 7), first as an FGF21 bolus of 3 mg/kg of body weight, followed 2 d later by a constant i.v. infusion of FGF21 at the rate of 6.3 mg/kg of metabolic body weight for 9 consecutive days. Biopsies of liver and adipose tissue were collected during the bolus phase of the experiment and used to analyze FGF21 signaling by Western blotting and expression of its receptor components by quantitative PCR. Bolus FGF21 administration caused a 4-fold increase in p44/42 MAPK (ERK1/2) activation in adipose tissue but had no effect on AKT and signal transducer and activator of transcription-3 (STAT3) signaling. The liver expressed negligible levels of the preferred FGF21 receptor FGFR1c and failed to mount any FGF21 signaling response. The FGF21 administered as a bolus had no effect on plasma glucose or insulin and did not stimulate an acute release of adiponectin from adipose tissue. Similarly, FGF21 infusion had no effect on plasma levels of glucose or insulin measured over the 9-d infusion or on glucose disposal during an i.v. glucose tolerance test performed on d 8 of infusion. Finally, the chronic FGF21 infusion had no effect on indices of adiponectin production, including plasma adiponectin and adipose tissue mRNA abundance of adiponectin and the endoplasmic reticulum chaperones ERO1A and DSBA-L involved in the assembly of adiponectin into multimeric complexes. These data show that human FGF21 does not act as an insulin sensitizer during the energy and glucose deficit of early lactation but do not rule out such a role in other physiological states.
    MeSH term(s) Adiponectin/blood ; Adiponectin/genetics ; Adiponectin/metabolism ; Adipose Tissue/metabolism ; Animals ; Blood Glucose/analysis ; Cattle/physiology ; Female ; Fibroblast Growth Factors/administration & dosage ; Humans ; Hyperinsulinism/veterinary ; Insulin/blood ; Insulin Resistance ; Lactation ; Liver/metabolism ; Random Allocation ; Recombinant Proteins ; Signal Transduction
    Chemical Substances Adiponectin ; Blood Glucose ; Insulin ; Recombinant Proteins ; fibroblast growth factor 21 ; Fibroblast Growth Factors (62031-54-3)
    Language English
    Publishing date 2019-09-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 242499-x
    ISSN 1525-3198 ; 0022-0302
    ISSN (online) 1525-3198
    ISSN 0022-0302
    DOI 10.3168/jds.2019-16695
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: ERAD deficiency promotes mitochondrial dysfunction and transcriptional rewiring in human hepatic cells.

    Liu, Qingqing / Yang, Xiaoqin / Long, Guangyu / Hu, Yabing / Gu, Zhenglong / Boisclair, Yves R / Long, Qiaoming

    The Journal of biological chemistry

    2020  Volume 295, Issue 49, Page(s) 16743–16753

    Abstract: Mitochondrial dysfunction is associated with a variety of human diseases including neurodegeneration, diabetes, nonalcohol fatty liver disease (NAFLD), and cancer, but its underlying causes are incompletely understood. Using the human hepatic cell line ... ...

    Abstract Mitochondrial dysfunction is associated with a variety of human diseases including neurodegeneration, diabetes, nonalcohol fatty liver disease (NAFLD), and cancer, but its underlying causes are incompletely understood. Using the human hepatic cell line HepG2 as a model, we show here that endoplasmic reticulum-associated degradation (ERAD), an ER protein quality control process, is critically required for mitochondrial function in mammalian cells. Pharmacological inhibition or genetic ablation of key proteins involved in ERAD increased cell death under both basal conditions and in response to proinflammatory cytokines, a situation frequently found in NAFLD. Decreased viability of ERAD-deficient HepG2 cells was traced to impaired mitochondrial functions including reduced ATP production, enhanced reactive oxygen species (ROS) accumulation, and increased mitochondrial outer membrane permeability. Transcriptome profiling revealed widespread down-regulation of genes underpinning mitochondrial functions, and up-regulation of genes associated with tumor growth and aggression. These results highlight a critical role for ERAD in maintaining mitochondrial functional and structural integrity and raise the possibility of improving cellular and organismal mitochondrial function via enhancing cellular ERAD capacity.
    MeSH term(s) Adenosine Triphosphate/metabolism ; Apoptosis/drug effects ; Cell Survival/drug effects ; Down-Regulation ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum-Associated Degradation/genetics ; Gene Editing ; Hep G2 Cells ; Humans ; Interleukin-12/pharmacology ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/genetics ; Mitochondria/metabolism ; Proteins/genetics ; Proteins/metabolism ; Reactive Oxygen Species/metabolism ; Transcriptome ; Tumor Necrosis Factor-alpha/pharmacology ; Up-Regulation
    Chemical Substances Proteins ; Reactive Oxygen Species ; SEL1L protein, human ; Tumor Necrosis Factor-alpha ; Interleukin-12 (187348-17-0) ; Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2020-09-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA120.013987
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The acute phase protein orosomucoid 1 is upregulated in early lactation but does not trigger appetite-suppressing STAT3 signaling via the leptin receptor.

    McGuckin, M M / Giesy, S L / Davis, A N / Abyeta, M A / Horst, E A / Saed Samii, S / Zang, Y / Butler, W R / Baumgard, L H / McFadden, J W / Boisclair, Y R

    Journal of dairy science

    2020  Volume 103, Issue 5, Page(s) 4765–4776

    Abstract: Dairy cows consume inadequate amounts of feed in early lactation and during conditions and diseases such as excessive fatness, heat stress, and infectious diseases. Affected cows often experience increases in plasma concentrations of acute phase proteins ...

    Abstract Dairy cows consume inadequate amounts of feed in early lactation and during conditions and diseases such as excessive fatness, heat stress, and infectious diseases. Affected cows often experience increases in plasma concentrations of acute phase proteins consistent with the negative effect of inflammation on appetite. The acute phase protein orosomucoid 1 (ORM1), also known as alpha-1-acid glycoprotein, was recently reported to reduce appetite in the mouse through its ability to bind the full-length leptin receptor (Ob-Rb) and activate appetite-suppressing signal transducer and activator of transcription 3 (STAT3) signaling. These observations raise the possibility that ORM1 exerts appetite-suppressing effects in dairy cattle during periods of increased inflammatory tone. The applicability of this model was assessed in 2 ways. First, we asked whether ORM1 is regulated during periods of inadequate appetite such as the transition from late pregnancy to early lactation and periods of increased inflammatory tone. Plasma ORM1 was invariant in late pregnancy but increased 2.5-fold between parturition and d 7 of lactation. Gene expression studies showed that liver was the major source of this elevation with little contribution by adipose tissue or mammary gland. Additional studies showed that plasma ORM1 was not increased further by excessive fatness or by reproductive dysfunction in early lactation and was completely unresponsive to inflammatory stimuli such as heat stress or intravascular administration of the endotoxin lipopolysaccharide during established lactation. Second, we tested the ability of ORM1 to trigger STAT3 signaling through Ob-Rb using Chinese hamster ovary K1 (CHO-K1) cells transfected with a STAT3 expression plasmid. In this configuration, CHO-K1 cells did not express Ob-Rb and were incapable of leptin-induced STAT3 phosphorylation. Leptin responsiveness was conferred by co-transfecting with bovine Ob-Rb, with leptin causing increases of 5.7-fold in STAT3 phosphorylation and 2.1-fold in the expression of the STAT3-dependent gene, SOCS3. In contrast, neither bovine or human ORM1 triggered STAT3 phosphorylation irrespective of dose and period of incubation tested. In summary, bovine ORM1 is not increased during periods of increased inflammatory tone except in early lactation and is incapable of Ob-Rb-dependent STAT3 signaling. Overall, these data are inconsistent with ORM1 mediating the appetite-suppressing effects of inflammation in cattle through Ob-Rb.
    MeSH term(s) Acute-Phase Proteins/metabolism ; Adipose Tissue/metabolism ; Animals ; Appetite Regulation/physiology ; CHO Cells ; Cattle/metabolism ; Cricetinae ; Cricetulus ; Female ; Lactation/physiology ; Leptin/metabolism ; Orosomucoid/metabolism ; Pregnancy ; Receptors, Leptin/metabolism ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Up-Regulation
    Chemical Substances Acute-Phase Proteins ; Leptin ; Orosomucoid ; Receptors, Leptin ; STAT3 Transcription Factor
    Language English
    Publishing date 2020-03-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 242499-x
    ISSN 1525-3198 ; 0022-0302
    ISSN (online) 1525-3198
    ISSN 0022-0302
    DOI 10.3168/jds.2019-18094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Effects of recombinant bovine interleukin-8 (rbIL-8) treatment on health, metabolism, and lactation performance in Holstein cattle III: Administration of rbIL-8 induces insulin resistance in bull calves

    Zinicola, M / Bicalho, R.C / Boisclair, Y / Menta, P.R / Ribeiro, B.L

    American Dairy Science Association Journal of dairy science. 2019 Nov., v. 102, no. 11

    2019  

    Abstract: Our previous work has suggested that recombinant bovine interleukin-8 (rbIL-8) treatment might influence cow metabolism. Therefore, this study was conducted to initially assess the effects of systemic administration of rbIL-8 on response to a glucose ... ...

    Abstract Our previous work has suggested that recombinant bovine interleukin-8 (rbIL-8) treatment might influence cow metabolism. Therefore, this study was conducted to initially assess the effects of systemic administration of rbIL-8 on response to a glucose challenge, blood metabolites, insulin, growth hormone, insulin-like growth factor-1, immune cell populations, and inflammatory parameters in Holstein bull calves. Calves from 30 ± 6 d of life were individually housed and randomly allocated to 1 of 2 treatment groups: rbIL-8 (rbIL-8, n = 10) and control (CTR, n = 8). Calves assigned to the rbIL-8 group received 1 s.c. injection (d 1, 0900 h) and 6 i.v. injections (d 1 at 1600 h, d 2 and 3 at 0900 h and 1600 h, and d 4 at 0900 h) of rbIL-8 (4 μg/kg of body weight), whereas the CTR group received 2 mL of sterile saline solution at each time point. Day of enrollment was considered as d 1, and the study duration was 10 d. Insulin concentrations and whole-body glucose disappearance were evaluated by an i.v. glucose tolerance test conducted at 12 h and 7 d following the last rbIL-8 injection. Rectal temperature and blood samples were collected on d 1, 2, 3, and 4 at −30 (before treatment, 0830 h), 30, 60, 120, 240, and 360 min relative to treatment, and daily at 0830 h for the rest of the study period. Serum was harvested, and the following parameters were measured: β-hydroxybutyrate (BHB), nonesterified fatty acids, glucose, insulin, plasma urea nitrogen, haptoglobin, and differential blood count. Significant differences were considered when P ≤ 0.05 and a trend if 0.05

    Keywords 3-hydroxybutyric acid ; blood glucose ; blood sampling ; blood serum ; body weight ; bulls ; calves ; cows ; free fatty acids ; glucose ; glucose tolerance tests ; granulocytes ; haptoglobins ; Holstein ; inflammation ; insulin ; insulin resistance ; insulin-like growth factor I ; interleukin-8 ; lactation ; lymphocytes ; metabolism ; monocytes ; sodium chloride ; somatotropin ; temperature ; urea nitrogen
    Language English
    Dates of publication 2019-11
    Size p. 10329-10339.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 242499-x
    ISSN 1525-3198 ; 0022-0302
    ISSN (online) 1525-3198
    ISSN 0022-0302
    DOI 10.3168/jds.2019-16336
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Insensitivity of well-conditioned mature sheep to central administration of a leptin receptor antagonist.

    Foskolos, A / Ehrhardt, R A / Hileman, S M / Gertler, A / Boisclair, Y R

    Animal : an international journal of animal bioscience

    2015  Volume 9, Issue 11, Page(s) 1852–1858

    Abstract: Ruminants remain productive during the energy insufficiency of late pregnancy or early lactation by evoking metabolic adaptations sparing available energy and nutrients (e.g. higher metabolic efficiency and induction of insulin resistance). A deficit in ... ...

    Abstract Ruminants remain productive during the energy insufficiency of late pregnancy or early lactation by evoking metabolic adaptations sparing available energy and nutrients (e.g. higher metabolic efficiency and induction of insulin resistance). A deficit in central leptin signaling triggers these adaptations in rodents but whether it does in ruminants remains unclear. To address this issue, five mature ewes were implanted with intracerebroventricular (ICV) cannula in the third ventricle. They were used in two experiments with an ovine leptin antagonist (OLA) when well-conditioned (average body condition score of 3.7 on a 5 point scale). The first experiment tested the ability of OLA to antagonize leptin under in vivo conditions. Ewes received continuous ICV infusion of artificial cerebrospinal fluid (aCSF), ovine leptin (4 µg/h) or the combination of ovine leptin (4 µg/h) and its mutant version OLA (40 µg/h) for 48 h. Dry matter intake (DMI) was measured every day and blood samples were collected on the last day of infusion. ICV infusion of leptin reduced DMI by 24% (P < 0.05), and this effect was completely abolished by OLA co-infusion. A second experiment tested whether a reduction in endogenous leptin signaling in the brain triggers metabolic adaptations. This involved continuous ICV infusions of aCSF or OLA alone (40 µg/h) for 4 consecutive days. The infusion of OLA did not alter voluntary DMI over the treatment period or on any individual day. OLA did not affect plasma variables indicative of insulin action (glucose, non-esterified fatty acids, insulin and the disposition of plasma glucose during an insulin tolerance test) or plasma cortisol, but tended to reduce plasma triiodothyronine and thyroxine (P < 0.07). Overall, these data show that a reduction of central leptin signaling has little impact on insulin action in well-conditioned mature sheep. They also raise the possibility that reduced central leptin signaling plays a role in controlling thyroid hormone production.
    MeSH term(s) Animal Feed ; Animals ; Blood Glucose/analysis ; Fatty Acids, Nonesterified/blood ; Female ; Infusions, Intraventricular ; Insulin/blood ; Leptin/administration & dosage ; Leptin/antagonists & inhibitors ; Random Allocation ; Receptors, Leptin/antagonists & inhibitors ; Receptors, Leptin/genetics ; Receptors, Leptin/metabolism ; Sheep/physiology ; Signal Transduction
    Chemical Substances Blood Glucose ; Fatty Acids, Nonesterified ; Insulin ; Leptin ; Receptors, Leptin
    Language English
    Publishing date 2015-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2257920-5
    ISSN 1751-732X ; 1751-7311
    ISSN (online) 1751-732X
    ISSN 1751-7311
    DOI 10.1017/S1751731115001159
    Database MEDical Literature Analysis and Retrieval System OnLINE

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