Influnce of niacin on lipide profile and metabolic adaptation in dairy cows during early lacttion

Cilj ove disertacije je da se ispita uticaj aplikacije niacina na metabolizam lipida u peripartalnom periodu, da se utvrdi dali aplikacija niacina utiče na insulinsku rezistenciju, vezu između metaboličkih parametara i lipolize i ketogeneze i uticaj aplikacije niacina na koncetracije NAD i NADP. NAD i NADP predstavljaju adekvatne pokazatelje statusa niacina kod krava u ranoj laktaciji, a njihova vrednost je značajno viša kod krava koje su primale ovaj vitamin. NED i NADP pokazuju pozitivnu korelaciju. Pored ovoga izvedene vrednosti kao što je NAD:NADP indeks i površina ispod krive koju prave ovi vitameri posle teljnja zavise od aplikacije niacina. Aplikacija niacina dovodi do smanjenja koncentracije NEFA, BHB i MDA, a do povećanja koncentracije triglicerida i holesterola u krvi krava. Aplikacija niacina dovodi do porasta koncentracije insulina i glukoze kod krava posle teljenja. Uticaj niacina na insulinsku rezistenciju se mora dvojako posmatrati. Krave koje primaju niacin imaju nižu vrednost indeksa glukoza:insulin, što znači da se po jedinici insulina neutrališe manje glukoze. Ovakvo stanje nastaje jer sa porastom koncentracije insulina opada njegova efikasnost i životinje ulaze u insulinsku rezustenciju. Međutim, RQUICKIBHB indeks insulinske rezistencije je pokazao da su krave koje su primale niacin mnogo osetljivije na insulin, što se može pripisati povećanoj insulinskoj senzitivnosti masnog tkiva. Kod krava koje su primale niacin nađena je niža koncentracija bilirubina i aktivnost AST, ALP i GGT. Nađena je viša koncentracija albumina i viša koncentracija uree i niža koncentracija fosfora. Rezultati pokazuju da aplikacija niacina pozitivno utiče na status hepatocita, a može uticati i na metabolizam proteina u organizmu zbog promena u vrednosti uree. Promena metaboličkih parametara posle teljenja išla je u istom pravcu u oglednoj i kontrolnog grupu, samo se menjao intenzitet promena u funkciji aplikacije niacina. Parcijalna korelacija pokazuje da vitameri niacina mogu objasniti određeni deo korelacije koji postoji između lipolize, ketogeneze i metaboličkim parametrima. Stopa promene veze između 142   metaboličkih parametara sa NEFA i BHB zavisi od stope promene statusa niacina u organizmu krava u ranoj laktaciji. Naknadnim istraživanjima treba odrediti kauzalnu prirodu ovih veza. Krave koje su primale niacina pokazivale su tendenciju povećane proizvodnje mleka do 30. dana laktacije. Ovakav uticaj niacina se izgubio prilikom merenja u 60. danu laktacije. Krave sa boljim statusom niacina (viša vrednost NAD i NADP) pokazuju manji stepen zamašćenja i bolju vitalnost hepatocita, a nađen je i veći dijametar adipocita u potkožnom  masnom  tkivu, što se može pripisati antilipoliznom efektu niacina.AB  The aim of this dissertation is to examine the effect of niacin on lipid metabolism in perpaturient period, to determine does application of niacin have effects on insulin resistance, relationship between metabolic parameters and lipolysis and ketogenesis and effects of application of niacin on NAD and NADP concentration in plasma. NAD and NADP present the adequate indicator of the status of niacin in cows in early lactation, and concentration of NAD and NADP is significant increase in cows that were treated with niacin. NAD and NADP demonstrate positive correlation. Despite this, the derived values like NAD:NADP ratio and area under the curve depends of the application of niacin. Application of niacin leads to decreased NEFA, BHB and MDA plasma concentration, and increased triglyceride and cholesterol concentration in plasma in cows. Application of niacin leads to increased concentration of insulin and glucose in plasma after partum. The effect of niacin on insulin resistance may have two sides. Cows that received niacin had lower value of  glucose:insulin ratio, that means that one unit of insulin metabolized less glucose. This state became because with increased insulin concentration decreased its efficiency and animals obtained insulin resistance. On the other hand index RQUICKIBHB for insulin resistance showed that cows that received niacin were much more sensitive to insulin, and that may be as a result of increased insulin sensitivity in adipose tissue.  Cows that have received niacin bilirubin concentration and activity of AST, ALP and GGT were decrease. Albumin concentration was increased, urea and phosphor concentration was decreased in group that had received niacin. Results indicate that application of niacin have positive impact on status hepatocytes, and may have influence on protein metabolism in organism because of alteration on value in urea. In control and niacin group alteration on metabolic parameters after partum went on the same direction, but intensity of changing was in function of application of niacin. Partial correlation indicates that niacin vitamers may explain certain part of correlation that exists between lipolysis, ketogenesis, and metabolic parameters.  Rate changes of the relationship between metabolic parameters with NEFA  and BHB depends of the rate changes of the niacin status in cows in early lactation. Subsequent research should determinate the causal nature of this relationship. Cows that have received niacin were demonstrating tendency of increased milk production until 30.day lactation. This impact of niacin was lost in 60.day of lactation. Cows with better status niacin (greater value of NAD and NADP) manifest smaller grade of hepatic lipidosis and better vitality of hepatocytes, and was found bigger 145   diameter on subcutaneous adipocytes, which can be as a result of antilipolitic effects of niacin

Niacin, Metabolic Stress and Insulin Resistance in Dairy Cows

The periparturient period in cows is associated with metabolic stress and a state of negative energy balance, which are characterized by increased lipolysis, ketogenesis, hepatic steatosis, oxidative stress and insulin resistance. Such metabolic changes may exert adverse effects on the health and milk yield of lactating cows. The pharmacokinetics of niacin in ruminants is specific as rumen microorganisms facilitate both the synthesis of tryptophan and the degradation of niacin. Niacin administration to cows leads to an increase in the coenzyme activity, encompassing the activity of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). These coenzymes are actively involved in the metabolism of lipids and carbohydrates, whereas NAD protects the organism from oxidative stress. In periparturient cows, the supplementation of niacin has been found to induce depressed lipolysis and a limited impact of nonesterified fatty acids on all metabolic processes. It also results in decreased lipid peroxidation regardless of the magnitude of lipolysis in the periparturient period. Furthermore, niacin reduces the concentration of ketone bodies, thus preventing the development of fatty lever disease and ketosis in cows. The anti-inflammatory effect of niacin is manifested in stimulating the secretion of adiponectin and inhibiting immune cells

The Effect of Niacin Application on the Development of Inflammation and Cholesterol Metabolism in Cows in Early Lactation

Cilj ovog rada je da se utvrdi uticaj niacina na metabolizam holesterola i ispita kako se istraživani uticaj odražava na zapaljenske procese i funkcionlani status jetre kod krava u ranoj laktaciji. Ogled je izvršen na 30 krava Holštajn-frizijske rase: 15 koje su primale niacin i 15 krava u negativnoj kontroli. Niacin je aplikovan u periodu dve nedelje pre i dve nedelje posle teljenja. Krv je uzimana venepunkcijom v.coccigea kod krava u periodu pre jutarnjeg hranjenja, u momentu teljenja, potom jednu i dve nedelje nakon teljenja. Aplikacija niacina dovodi do smanjenja koncentracije tumor necrosis factor alpha (TNF-α), haptoglobina i nonesterified fatty acid (NEFA), dok na vrednosti fibrinogena nije pokazao značajan efekat. Aplikacija niacina povećava vrednost holesterola, albumina i smanjuje vrednost bilirubina, što je znak boljeg funkcionalnog stanja hepatocita. Niacin pored antilipolitičkog efekta, pokazuje i antiinflamatorni efekat koji može biti značaj mehanizam u zaštiti hepatocita u ranoj laktaciji kod mlečnih krava. Od velikog značaja se pokazao uticaj niacina na TNF-α, jer ovaj citokin kontroliše korelaciju između lipolize i metabolizma holesterola sa inflamatornim odgovorom, posmatrano kroz indeks funkcionalnog statusa jetre.The aim of this study is to determine the effect of niacin on cholesterol metabolism and functional liver status in cows in early lactation. The experiment was performed on 30 Holstein-Friesian cows: 15 receiving niacin and 15 cows in negative control. Niacin was administered for two weeks before and two weeks after calving. Blood was taken by venipuncture of v.coccigea in cows before feeding in the morning, at the time of calving, and then one and two weeks after calving. Niacin administration reduced the concentration of tumor necrosis factor alpha (TNF-α), haptoglobin and nonesterified fatty acid (NEFA), while it showed no significant effect on fibrinogen values. Niacin administration increases cholesterol, albumin, and bilirubin levels, which is a sign of a better functional state of hepatocytes. Niacin, in addition to its antilipolitic effect, also exhibits an anti-inflammatory effect, which may be a significant mechanism in the protection of hepatocytes in early lactation in dairy cows. The influence of niacin on TNF-α has been shown to be of great importance, as this cytokine controls the correlation between lipolysis and cholesterol metabolism with an inflammatory response, viewed through an index of liver functional status

Efekat niacina u regulaciji metabolizma krava u ranoj laktaciji

Niacin is of great importance for the energy metabolism, because it is incorporated in the coenzyme nicotinamide adenine dinucleotide (NAD), which participates in a number of oxidative-reduktacionih reactions in anabolic pathways (NADPH/NADP) and catabolic pathways (NADH/NAD). Niacin, which is administered orally can be found as a rumen not protected niacin or rumen protected niacin. Encapsulated technology can dramatically increase bioavailability of components in the small intestine. By reducing the concentration of NEFA in cows fed rumen protected with niacin postpartum is possible lead to a reduction in accumulation and triglycerides. Insulin is involved in the reaction of niacin with glucose in the blood. Due to the above niacin can play an important role in the regulation of metabolic stress in cows in early lactation. A potential mechanism through which niacin exerts its effect on lipid metabolism is reflected in its impact on insulin resistance in cows.Niacin je od velike važniosti za energetski metabolizam, zato što se inkorporira u koenzimu nicotinamid adenin dinukleotid (NAD) koji učestvuje u velikom broju oksidativno-reduktacionih reakcija: u anaboličkim putevima (NADPH/NADP) i kataboličkim putevima (NADH/NAD). Niacin koji se aplicira oralno može se naći kao rumen ne zaštičeni niacin ili rumen zaštičeni niacin. Inkapsulirana tehnologija može dramatično povečati bioraspoložlivost komponenata u tankim crevima. Reduciranjem koncentracija ne-estrikofanih viših masnih kiselina (NEFA) kod krava hranjenim sa rumen zaštičenim niacinom postpartum moguće je dovesti do smanjenje akumulacije i triglicerida. Insulin je involviran u reakciji niacina sa glukozom u krvi. Zbog svega navedenog niacin može imati značajnu ulogu u regulaciji metaboličkog stresa kod krava u ranoj laktaciji. Potencijalni mehanizma preko kog niacin ispoljava svoj efekat na metabolizam lipida ogleda se u njegovom uticaju na insulinsku rezistenciju kod krava

Uticaj aplikacije Niacina u peripartalnom periodu krava na proizvodnju mleka do postizanja pika laktacije

The aim of this study is to determine whether the use of niacin in the peripartum affects milk production in cows in the initial niacin early laktaciji.15 cows and 15 cows were presented a negative control. Niacin is managed through food orally. We used a preparation in a dose that allows access to the intestine, about 6-12g niacin / day. The application of niacin tendency towards positive action on the production of milk for 30 days of lactation (p <0.1), but this trend is lost if we look at a longer period from birth to 60.dana lactation. Although there were no statistically significant differences in milk production, from a practical point of view, it is important to determine the percentage of cows in the group who received niacin that had statistically significant higher milk production than in a group that did not get niacin. The analysis of frequency allocation, beta fixes and statistical power of the test is calculated that 60% of the cows showed significantly higher production of milk cows in the group who received niacin compared to control, but with the progress of lactation, this percentage decreases, and 60 days of lactation have only 26 , 6% of cows that are significantly higher milk production compared to the control. The use of niacin can improve milk production in cows in early lactation.Cilj ovog rada je da se utvrdi da li aplikacija niacina u peripartalnom periodu utiče na proizvodnju mleka kod krava u ranoj laktaciji.15 krava je primal niacin, a 15 krava su predstavljane negativnu kontrolu. Niacin je aplikovan putem hrane per os. Korišćen je preparat u dozi koja omogućuje dostupnost u crevima oko 6-12g niacina/dan. Aplikacija niacina pokazuje tendenciju pozitivnog delovanja na proizvodnju mleka do 30. dana laktacije (p<0,1), ali se ova tendencija gubi ako posmatramo širi period od partusa do 60.dana laktacije. Iako nije bilo statistički značajne razlike u proizvodnji mleka, sa praktičnog aspekta je značajno odrediti koji je to procenat krava u grupi koja je primala niacin koji je imao statistički značajno veću proizvodnju mleka u odnosu na grupu krava koja nije primala niacin. Analizom distribucija frekvencije, beta greške i statističke snage testa izračunato je da je 60% krava pokazalo statistički značajno veću proizvodnju mleka u grupi krava koja je primala niacin u odnosu na kontrolu, ali se sa napredovanjem laktacije taj procenat smanjuje, pa 60. dana laktacije imamo samo 26,6% krava koje su pokazale značajno veću proizvodnju mleka u odnosu na kontrolu. Upotreba niacina može poboljšati proizvodnju mleka kod krava u ranoj laktaciji

Influence of niacin administration on lipid peroxidation in cows in early lactation

Niacin is a reactive part of NAD and NADP, which are co-enzymes in numerous oxidative and reductive reactions. In early lactation, there is an increased lipid mobilization, accompanied by inflammatory response and oxidative stress. The aim of this study was to examine the effect of niacin administration in cows during early lactation in reducing lipid peroxidation i.e. MDA (malondialdehyde) concentration. Niacin was administered through feed two weeks before and two weeks after calving. Blood samples were taken in the week preceding calving and in the first and second week after calving. MDA concentration was significantly lower in cows receiving niacin compared to the control group during all three samplings: 1.89±0.33:1.42±0.13 (calving, week 0); 2.37±0.41:1.64±0.15 (first week) and 2.6±0.45:1.8±0.17µmol/L (second week). In control cows, no significant correlation between MDA and NEFA concentrations was found compared to cows fed niacin. In cows receiving niacin, the concentration of MDA linearly increased, as did the NEFA concentration. Niacin supplementation in early lactation can decreaselipid peroxidation in cows. Reduced lipid peroxidation in cows can be a consequence of the antilipolytic effect of niacin

UTICAJ APLIKACIJE NIACINA NA LIPIDNU PEROKSIDACIJU KOD KRAVA U RANOJ LAKTACIJI

Niacin is a reactive part of NAD and NADP, which are co-enzymes in numerous oxidative and reductive reactions. In early lactation, there is an increased lipid mobilization, accompanied by inflammatory response and oxidative stress. The aim of this study was to examine the effect of niacin administration in cows during early lactation in reducing lipid peroxidation i.e. MDA (malondialdehyde) concentration. Niacin was administered through feed two weeks before and two weeks after calving. Blood samples were taken in the week preceding calving and in the first and second week after calving. MDA concentration was significantly lower in cows receiving niacin compared to the control group during all three samplings: 1.89±0.33:1.42±0.13 (calving, week 0); 2.37±0.41:1.64±0.15 (first week) and 2.6±0.45:1.8±0.17µmol/L (second week). In control cows, no significant correlation between MDA and NEFA concentrations was found compared to cows fed niacin. In cows receiving niacin, the concentration of MDA linearly increased, as did the NEFA concentration. Niacin supplementation in early lactation can decreaselipid peroxidation in cows. Reduced lipid peroxidation in cows can be a consequence of the antilipolytic effect of niacin.Accepted for publishin

INFLUENCE OF NIACIN APPLICATION ON THE VALUE OF ITS VITAMERS IN THE BLOOD OF COWS IN EARLY LACTATION

Vitamin niacin is of great importance for energy metabolism. Physiological niacin is incorporated into the coenzyme nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The aim of this study was to determine the concentration of NAD and NADP in the blood of cows during the application of niacin in the peripartum period. The value of these vitamins depends on the peripartum week, regardless of the constant exogenous source of niacin.Publishe