14 research outputs found
Einfluss des Flavonols Quercetin auf Glucosestoffwechsel und Gesundheits- status beim neugeborenen Kalb
With birth, calves are confronted with a new, extrauterine environment and
have to meet their energy demand autonomously. For this reason, it is
essential that not only overall energy intake, but also endogenous glucose
production work effectively, because glucose is one of the main energy sources
during the first stage of life. With the intake of first colostrum calves
ingest not only nutrients, but also a plethora of bioactive factors which
support the maturation and development of metabolic processes. Colostrum is
further essential to support the naïve immune system of newborn calves during
the first weeks of life and to mediate passive immunity. Unfortunately,
colostrum supply is often inadequate. To support the health status, flavonoids
could play an important role in the upbringing of newborn calves. These are
secondary plant metabolites with numerous attributed health-promoting
properties. One of the most important flavonoids is quercetin, which is proven
to possess antioxidative, anti-inflammatory and antimicrobial capacity and to
modulate the intestinal microflora. However, quercetin also interacts with
glucose metabolism by inhibiting intestinal carbohydrate absorption and
reducing plasma glucose concentrations. For newborn calves, such an effect
would be crucial. Therefore, it was the main objective of the present work to
investigate the effects of an oral quercetin supplementation on the glucose
metabolism of newborn calves, because this knowledge would be the prerequisite
to consider the usage of quercetin as a health promoting feed additive in calf
rearing. In the first part of the study, 28 newborn male Holstein Friesian
calves were assigned to two dietary groups and fed colostrum or a milk-based
formula with same macronutrient composition, but without bioactive factors,
during the first two days of life. On d 2 of life, groups were subdivided into
control and treatment groups, the latter receiving quercetin aglycone with
meals during the first week of life. On d 3, intestinal xylose absorption was
probed, on d 7, a tracer study was conducted to investigate the first pass
uptake of glucose, and on d 8, a liver biopsy sample was taken and analyzed
via PCR. The postabsorptive recovery rate of orally administered xylose and
13C6-labelled glucose in plasma was higher in calves that initially received
colostrum, indicating a better intestinal absorption capacity and a lower
splanchnic glucose extraction when compared to colostrum-deprived calves.
Irrespective of quercetin supplementation, the mRNA abundance of hepatic
mitochondrial phosphoenolpyruvate carboxykinase and several plasma metabolites
were also reduced in formula-fed calves, pointing to a delayed maturation of
metabolic pathways after colostrum deprivation. Although quercetin-fed calves
initially showed higher peak concentrations of 13C6-glucose in plasma on d 7,
this effect did not last for the following hours. Based on the finding that an
oral quercetin supplementation does not seem to disadvantage the glucose
metabolism in newborn calves, the health parameters recorded during the trial
were evaluated in the second part of this work. Additionally, plasma samples
of the calves were analyzed for concentrations of immunoglobulins, acute-phase
proteins, as well as parameters of the antioxidative system. Furthermore, the
expression of genes for some proinflammatory cytokines, antioxidative enzymes
and acute-phase proteins was analyzed in cDNA samples generated from the liver
biopsy tissue. Data indicate that an adequate initial colostrum supply
supports neonatal health and prepares the calves very well to cope with the
new environment. Colostrum-fed calves showed reduced signs of inflammation and
were more vital than calves initially fed formula, further, the metabolic
status was improved. In contrast to this, the quercetin supplementation did
not induce any detectable health-promoting effects, a finding that underlines
that results proven in vitro are not always transferable to the organism as a
whole. In summary, it can be concluded from the present work that an oral
quercetin supplemen-tation does not impair the glucose metabolism of newborn
dairy calves. However, health-promoting properties cannot be reproduced in
vivo, hence quercetin feeding cannot compensate for an inadequate initial
colostrum supply.Mit der Geburt werden Kälber mit einer neuen, extrauterinen Umgebung
konfrontiert und müssen ihren Energiebedarf selbstständig decken. Dafür ist es
essentiell, dass nicht nur ausreichend Nährstoffe aufgenommen werden, sondern
auch die endogene Glucosepro-duktion effizient funktioniert, da Glucose in der
ersten Lebensphase als eine Hauptenergie-quelle dient. Mit der Aufnahme von
Kolostrum werden neben Nährstoffen auch zahlreiche bioaktive Substanzen
zugeführt, die die Reifung und Entwicklung von Stoffwechselprozessen fördern.
Kolostrum ist außerdem essentiell, um das naive Immunsystem des Kalbes während
der ersten Lebenswochen zu unterstützen und passive Immunität zu vermitteln.
Leider ist die Kolostrumversorgung oft suboptimal. Um die Gesundheit zu
fördern, könnte dem Einsatz von Flavonoiden hier eine wichtige Rolle zukommen.
Es handelt sich dabei um sekundäre Pflanzenstoffe, denen zahlreiche
gesundheitsfördernde Eigenschaften zugeschrieben werden. Einer der
Hauptvertreter ist Quercetin, welches nachweislich antioxidativ, anti-
inflammatorisch und antimikrobiell wirken und die Darmflora modulieren kann.
Allerdings interagiert es auch mit dem Glucosestoffwechsel, wodurch die
intestinale Aufnahme sowie der Blutglucosespiegel gesenkt werden. Für das Kalb
wäre dies fatal. Somit war es das Hauptziel dieser Arbeit, die Wirkung einer
oralen Quercetinsupplementierung auf den Glucosestoffwechsel neugeborener
Kälber zu untersuchen, da die Kenntnis darüber die Voraussetzung ist, um den
Einsatz von Quercetin als gesundheitsfördernden Futter-zusatzstoff in der
Kälberaufzucht überhaupt in Betracht ziehen zu können. Zu diesem Zweck wurden
28 neugeborene männliche Kälber der Rasse Deutsche Holstein in zwei
Fütterungsgruppen unterteilt und während der ersten beiden Lebenstage entweder
mit Kolostrum oder einer Formula mit gleicher Makronährstoffzusammensetzung,
jedoch ohne bioaktive Substanzen, gefüttert. Am 2. Lebenstag erfolgte eine
Unterteilung in Kontroll- und Behandlungsgruppen, wobei letztere während der
ersten Lebenswoche Quercetin mit der Fütterung erhielten. Am 3. Lebenstag
wurde eine Xyloseabsorptionsstudie durchgeführt, am 7. Lebenstag erfolgte eine
Tracerstudie zum first pass uptake von Glucose, und am 8. Tag wurde
Lebergewebe mittels Biopsie entnommen und mit Hilfe von PCR analysiert. Die
postabsorptive Wiederfindung von oral verabreichter Xylose und 13C6-markierter
Glucose im Plasma war höher in initial Kolostrum-gefütterten Kälbern, was im
Vergleich zu Formula-gefütterten Tieren auf eine bessere Absorptionskapazität
sowie eine geringere Glucoseextraktion im Splanchnikusgewebe schließen lässt.
Ferner waren die mRNA Abundanz der hepatischen mitochondrialen
Phosphoenolpyruvatcarboxykinase sowie verschiedene Plasmametaboliten in den
Formulagruppen unabhängig von der Quercetin-supplementierung reduziert, was
auf eine verzögerte Reifung des Stoffwechsels nach Kolostrumentzug hindeutet.
Obwohl die Quercetinsupplementierung am 7. Lebenstag den intestinalen
Glucoseabsorptionspeak steigern konnte, verlor sich dieser Effekt im Verlauf
der darauffolgenden Stunden. Basierend darauf, dass eine orale
Quercetinsupplementierung den Glucosestoffwechsel bei neugeborenen Kälbern
nicht nachteilig beeinflusst, wurden im zweiten Teil der Arbeit die während
der Studie aufgenommenen Gesundheitsparameter genauer ausgewertet. Weiterhin
wurden Plasmaproben der Tiere auf Konzentrationen von Immunglobulinen, Akute-
Phase-Proteinen sowie auf Parameter des antioxidativen Systems untersucht und
die Genexpression verschiedener proinflammatorischer Zytokine, antioxidativer
Enzyme und akuter-Phase-Proteine in den zuvor angelegten cDNA Umschreibungen
analysiert. Die Ergebnisse zeigten, dass die adäquate Versorgung mit Kolostrum
während der ersten Lebenstage die Kälber gut für die erste Lebensphase
ausstattet und die Kälbergesundheit fördert. Die Tiere zeigten verminderte
Anzeichen von Inflammation und waren in den ersten Lebenstagen vitaler als
Kälber der Formulagruppe, ferner war der metabolische Status verbessert. Die
Quercetinsupplementierung hingegen brachte keine gesundheitsfördernden
Effekte, was beweist, dass in vitro nachgewiesene Effekte nicht auf den
Gesamtorganismus übertragbar sind. Zusammenfassend lässt sich aus dieser
Arbeit ableiten, dass die Fütterung von Quercetin Aglykon beim neugeborenen
Kalb zwar keine nachteiligen Effekte auf den Glucose-stoffwechsel hat. Dennoch
sind die gesundheitsfördernden Eigenschaften nicht in vivo reproduzierbar,
sodass der Einsatz von Quercetin als Futterzusatz keinesfalls eine
unzureichende Kolostrumversorgung kompensieren kann
Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits
Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight x day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1a, interleukin-1ß, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply
Effects of Feeding Milk Replacer Ad Libitum or in Restricted Amounts for the First Five Weeks of Life on the Growth, Metabolic Adaptation, and Immune Status of Newborn Calves
The pre-weaning period is critical for calf health and growth, and intensive milk feeding programs may assist postnatal development by improving body growth and organ maturation. The aim of the present work was to study the effects of ad libitum milk replacer (MR) feeding on the growth, metabolic adaptation, health, and immune status of newborn calves. Twenty-eight newborn Holstein and Holstein x Charolais crossbred calves were fed ad libitum (ADLIB) or in restricted amounts (6 liters per day; RES) during the first five weeks of life. The MR intake in the ADLIB treatment was gradually reduced at weeks 6 and 7, and all calves then received 6 liters of MR per day until day 60. Blood samples were collected to measure the plasma concentrations of metabolites, insulin, insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP), immunoglobulins, and acute phase proteins. The expression of mRNA associated with both the somatotropic axis and gluconeogenic enzymes was measured in the liver on day 60. Intensive feeding improved MR intake and growth in ADLIB without influencing concentrate intake. Carcass weight, perirenal fat, and muscle mass were greater in ADLIB. Plasma concentrations of glucose, triglycerides, insulin, and IGF-I were greater, whereas plasma concentrations of β-hydroxybutyrate, total protein, albumin, urea, IGFBP-2 and -4, and fibrinogen were lower at distinct time points in ADLIB. The hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase was greater in ADLIB. Most metabolic and endocrine differences occurred during the MR feeding period, but a slightly greater concentrate intake was associated with increased plasma IGF-I and insulin at the end of the study. The immune and health status of the calves were not affected by MR feeding. However, increased plasma fibrinogen in the RES group suggested differences in the acute phase response
Flavonol concentrations in plasma.
<p>Stacked concentrations (<b>A</b>) and percentage composition (<b>B</b>) of flavonols in basal plasma samples of calves fed either colostrum (dark grey) or formula (light grey) on days 1 and 2 and supplemented with quercetin aglycone from day 2 to day 8 (50 mg/(kg body weight × day)). Flavonol metabolites: quercetin (without symbol), isorhamnetin (horizontal line), tamarixetin (crossline) and kaempferol (horizontal bold line). Data are presented as the least squares means. Different uppercase letters (A, B, C) symbolize differences in the total flavonol concentration within the same group on different days (<i>P</i> < 0.05). † tend to differ among groups on the same day (<i>P</i> < 0.10).</p
Antioxidative Status in Plasma.
<p>Plasma parameters for antioxidative capacity (<b>A</b>, <b>B</b>) and oxidative stress (<b>C</b>, <b>D</b>) in calves fed either colostrum (dark grey) or formula (light grey) on days 1 and 2 and supplemented with (crossline) or without (no symbol) quercetin on days 2–8 (50 mg/(kg body weight × day)). Data are presented as the least squares means ± standard errors. Bars with different lowercase letters (a, b) differ among groups within the same day (<i>P</i> < 0.05). TEAC, trolox equivalent antioxidative capacity (in trolox equivalents, TE); FRAP, ferric reducing ability of plasma (in ascorbic acid equivalents, ASCE); TBARS, thiobarbituric acid reactive species (in malondialdehyde equivalents, MDAE).</p
Feed Intake and Growth Performance.
<p>Colostrum and milk replacer (MR) (<b>A</b>) and concentrate intake (<b>B</b>), total metabolizable energy (ME) intake, body weight (<b>D</b>), and average daily gain (<b>E</b>) in calves fed MR either <i>ad libitum</i> (ADLIB, black square, straight line) or restrictively (RES, white circle, dashed line) for the first five weeks of life. MR intake in ADLIB was gradually reduced during weeks 6 and 7 to amounts fed in RES. The data are presented as the least squares means ± standard error. <sup>†</sup>Trend between groups <i>P</i> < 0.1; *different between groups <i>P</i> < 0.05; **different between groups <i>P</i> < 0.01; and ***different between groups <i>P</i> < 0.001.</p
Endocrine Status in Blood Plasma.
<p>The plasma concentrations of insulin (<b>A</b>), insulin-like growth factor 1 (IGF-I; <b>B</b>), and IGF-binding proteins (IGFBP)-2 (<b>C</b>), -3 (<b>D</b>), and -4 (<b>E</b>) in calves fed milk replacer (MR) either <i>ad libitum</i> (ADLIB, black square, straight line) or restrictively (RES, white circle, dashed line) for the first five weeks of life. MR intake in ADLIB was gradually reduced during weeks 6 and 7 to amounts fed in RES. The data are presented as the least squares means ± standard error. <sup>†</sup>Trend between between groups <i>P</i> < 0.1, *different between groups <i>P</i> < 0.05, **different between groups <i>P</i> < 0.01, and ***different between groups <i>P</i> < 0.001.</p
Carcass Composition.
<p>The weight of the hot carcass, liver, pancreas, fat depots, and distinct muscle cuts<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168974#t003fn002" target="_blank"><sup>1</sup></a> and the size of the musculus longissimus dorsi (MLD) in calves fed milk replacer (MR) either <i>ad libitum</i> (ADLIB) or restrictively (RES) for the first five weeks of life.</p
Metabolic Status in Blood Plasma.
<p>The plasma concentrations of glucose (<b>A</b>), lactate (<b>B</b>), beta-hydroxybutyrate (BHB; <b>C</b>), non-esterified fatty acids (NEFA; <b>D</b>), triglycerides (<b>E</b>), and cholesterol (<b>F</b>) in calves fed milk replacer (MR) either <i>ad libitum</i> (ADLIB, black square, straight line) or restrictively (RES, white circle, dashed line) for the first five weeks of life. MR intake in ADLIB was gradually reduced during weeks 6 and 7 to amounts fed in RES. The data are presented as the least squares means ± standard error. <sup>†</sup>Trend between groups <i>P</i> < 0.1, *different between groups <i>P</i> < 0.05, **different between groups <i>P</i> < 0.01, and ***different between groups <i>P</i> < 0.001.</p