Selective abdominal venous congestion induces adverse renal and hepatic morphological and functional alterations despite a preserved cardiac function

Venous congestion is an important contributor to worsening renal function in heart failure and the cardiorenal syndrome. In patients, it is difficult to study the effects of isolated venous congestion on organ function. In this study, the consequences of isolated abdominal venous congestion on morphology and function of the kidneys, liver and heart were studied in a rat model. Twelve shamoperated (SHAM) male Sprague Dawley rats were compared to eleven inferior vena cava-constricted (IVCc) rats for twenty-one weeks. Abdominal venous pressure was significantly higher in the IVCc versus SHAM group (p < 0.0001). Indices of liver and kidney weight, function and morphology, inflammation as well as collagen deposition were significantly increased in the IVCc compared to SHAM group, (p < 0.05). Echocardiographic and hemodynamic parameters were largely unaffected by abdominal venous congestion. In this rat model of isolated abdominal venous congestion, retrogradely conducted glomerular hypertension without a concomitant change in glomerular filtration rate was observed. Adverse short-term hepatic morphological alterations were developed which explain the observed organ function dysfunction. Importantly, cardiac function remained comparable between both groups. This study provides relevant insight in the pathophysiology of abdominal congestion on organ function

The Role of Diet-induced Thermogenesis in the Regulation of Voluntary Feed Intake in the Chicken: Nutritional and Genetic Influences

De regeling van de vrijwillige voederopname is een complex mechanisme da t op verscheidene niveaus gecontroleerd wordt. Onderzoek heeft aangetoon d dat eetlust en verzadiging worden beïnvloed door voedingsfactoren zoal s de voedersamenstelling, en ook door genetische factoren. Voor zoogdier en werden meerdere modellen voorgesteld om de mechanismen te begrijpen d ie voederopname en energieverbruik op elkaar afstellen met het oog op he t behoud van de lichaamshomeostase. Bij deze diersoorten, inclusief de m ens, speelt de dieet-geïnduceerde thermogenese (DIT) een belangrijke rol in de controle en de regeling van de voederopname. Dit oorzakelijke ver band werd door Stubbs et al. (1997) vastgelegd in de zogenaamde hiëra rchische oxidatietheorie: eiwitten worden preferentieel geoxideerd, gevo lgd door koolhydraten en tenslotte vetten. Deze volgorde komt overeen me t de verzadigingscapaciteit van deze macronutriënten, hetgeen doet vermo eden dat macronutriënt-specifieke oxidatie een rol speelt in de regeling van de voederopname. Bij pluimvee is er echter weinig of geen inform atie beschikbaar over de rol van DIT in de controle van de vrijwillige v oederopname. Het nagaan of de hiërarchische oxidatietheorie ook geldt bi j deze diersoorten is dan ook meteen de hoofddoelstelling van voorliggen de studie. De rol van DIT in de controle en de regeling van de vrijwillige voederop name bij pluimvee werd bestudeerd aan de hand van uiteenlopende modellen : voedersamenstelling, genotype en de combinatie van beiden. Om de invlo ed van de macronutriëntenverhouding van het voeder na te gaan, werden proefvoeders samengesteld met een iso-energetische variatie van eiwitte n ten opzichte van vetten en met eenzelfde koolhydraatgehalte. Vleeskuik ens die gehouden werden op het voeder met een laag eiwitgehalte vertoond en een 13 % hogere DIT en een 24 % lagere voederopname vergeleken met vl eeskuikens die gehouden werden op het iso-energetische voeder met een la ag vetgehalte. Deze verschillen waren echter niet statistisch beduidend. Er werden evenmin effecten van de voedersamenstelling op de DIT of de v oederopname waargenomen bij vleeskuikens die geselecteerd werden op basi s van een hoog of laag gehalte aan los buikvet en die dezelfde iso-energ etische voeders kregen. Daarnaast werden kippen met genotypes die een verschil in voederefficiëntie induceren met elkaar vergeleken wanneer z e hetzelfde voeder aangeboden kregen. In een eerste studie werden opgroe iende hanen van een leglijn vergeleken met vleeskuikens van eenzelfde le eftijd. In een volgende studie werden volwassen hanen die geselecteerd w erden voor een hoge (R+) of een lage (R-) residuele voederopname aan elk aar getoetst. De DIT was significant hoger bij de inefficiënte genotypes (hanen van een leglijn en R+ hanen) vergeleken met de meer efficiënte g enotypes (vleeskuikens en R- hanen). Er werd echter geen beduidende teru gkoppeling van de DIT op de voederopname waargenomen, aangezien de ineff iciënte genotypes eveneens een grotere voederopname hadden. Deze resulta ten suggereren dat de DIT niet direct betrokken is bij de regeling van d e voederopname bij de gebruikte modellen. Toch speelt de voedersamenstel ling, en vooral het eiwitgehalte van het voeder een rol in de controle v an de voederopname. De vleeskuikens die het voeder met laag eiwitgehalte kregen, vertoonden een hogere voederopname om aan hun eiwitbehoeften te gemoet te komen. Ook het genotype had een duidelijk effect op voederopna me, als een directe selectierespons (R+ en R- hanen) of als een gecorrel eerde selectierespons (hanen van een leglijn en vleeskuikens). De methodologie om ademtesten met stabiele isotopen uit te voeren in com binatie met indirecte calorimetrie werd voor het eerst op punt gesteld v oor kippen. De technieken om de oxidatie van U-13C6-glucose en van 1-13C 1-kaliumpalmitaat evenals de decarboxylatie van 1-13C1-leucine te meten werden geoptimaliseerd en gevalideerd. De decarboxylatie van 1-13C1-leuc ine was statistisch beduidend lager bij vleeskuikens die werden gehouden op het voeder met laag eiwitgehalte vergeleken met de dieren gehouden o p het iso-energetische voeder met laag vetgehalte. De oxidatie van U-13C 6-glucose werd niet beïnvloed door de samenstelling van de iso-energetis che voeders, wat waarschijnlijk te verklaren is door het gelijke koolhyd raatgehalte in beide voeders. De R+ hanen vertoonden een significant hogere U-13C6-glucose oxidatie, w aarschijnlijk door hun hogere koolhydraatopname vergeleken met de R- han en. De decarboxylatie van 1-13C1-leucine was hoger bij de dieren met ine fficiënte genotypes vergeleken met de hanen met meer efficiënte genotype s, hoewel dit verschil niet significant was. De voedersamenstelling had een uitgesproken invloed op het gehalte aan m etabolieten in het plasma en op de lichaamssamenstelling. De vleeskuiken s die werden gehouden op het voeder met laag eiwitgehalte vertoonden een overdadige opname van energie ten opzichte van eiwit vergeleken met dit van vleeskuikens die het voeder met laag vetgehalte verstrekt kregen. H ierdoor waren de warmteproductie evenals de triiodothyronine-concentrati es in het plasma hoger bij de eerstgenoemde dieren. Daarnaast hadden dez e dieren een grotere energieretentie onder de vorm van vet vergeleken me t de vleeskuikens die werden gehouden op het voeder met laag vetgehalte. De lagere urinezuurconcentraties in het plasma van de vleeskuikens geho uden op het voeder met laag eiwitgehalte wijzen op een verminderde amino zuurdegradatie vergeleken met vleeskuikens die het voeder met laag vetge halte kregen. Deze veronderstelling wordt ondersteund door de lagere dec arboxylatie van 1-13C1-leucine door de vleeskuikens gehouden op het voed er met laag eiwitgehalte. Deze resultaten tonen aan dat er aminozuurspa rende mechanismen door deze vleeskuikens aangesproken worden, zowel op het niveau van vertering als op postabsorptief niveau. De metabolietconcentraties in het plasma van de hanen van de leglijn war en significant hoger dan die in het plasma van de vleeskuikens. Aangezie n de kippen van beide groepen werden gehouden op commerciële voeders bes temd voor vleeskuikens is dit mogelijk te wijten aan een relatief overaa nbod aan nutriënten bij de hanen van de leglijn. Bijgevolg kunnen deze v erschillen niet worden toegeschreven aan het genotype per se. De urin ezuurconcentraties waren hoger in het plasma van de inefficiënte R+ hane n vergeleken met de R- hanen, wat overeenkomt met de verhoogde decarboxy latie van 1-13C1-leucine in de R+ dieren. Een brede waaier aan modellen werd gebruikt om het effect van de macronu triënten-verhouding in het voeder, het genotype en de interactie tussen deze variabelen op de dieet-geïnduceerde thermogenese en de rol ervan in de controle en de regeling van de vrijwillige voederopname bij de kip t e bestuderen. De resultaten wijzen erop dat de dieet-geïnduceerde thermo genese geen belangrijke rol speelt in de regeling van de vrijwillige voe deropname bij deze modellen, dit in tegenstelling tot bij zoogdieren.status: publishe

Implications of dietary macronutrients for growth and metabolism in broiler chickens

In chickens, metabolism is influenced by environmental factors and of particular interest nutritional factors, such as diet quantity and composition. With respect to the dietary macronutrients, literature clearly shows that in isoenergetically formulated diets, the protein level has a pronounced effect on metabolism, whereas fat and carbohydrate concentrations play a limited role. A decreased dietary protein level results in depressed growth rates, with reduced carcass gains in both water and protein content. In spite of the lower protein retention in chickens fed low protein diets, the efficiency of utilization of dietary protein appears to be increased. This indicates an inverse relationship between protein intake and utilization, which is reflected in decreased circulating uric acid levels. In addition, feed intake is increased, at least when protein levels are slightly reduced, leading to an involuntary overconsumption of energy compared to protein. The chickens deal with this excess energy consumption by increasing de novo lipogenesis and fat deposition, which is supported by increased plasma triglyceride concentrations, and heat production is increased. In contrast to adult mammals, the dietary macronutrients have no effect on diet-induced thermogenesis, nor is there any relationship between diet-induced thermogenesis and feed intake. Plasma growth hormone levels are higher in chickens reared on a low protein diet, indicating a causal relationship between growth hormone secretion and protein efficiency. In spite of the increased growth hormone levels, plasma insulin-like growth factor concentrations are lowered in low protein reared chickens, and may be partially responsible for the reduced growth rate observed in these animals. Plasma corticosterone concentrations are augmented in chickens on low protein diets, despite a decline in the ACTH concentration. Finally, plasma T-3 and T-4 levels are well known to increase and decrease, respectively, with decreasing protein content, whereas the effects of dietary macronutrients on circulating leptin levels require more research.status: publishe

The effect of feed withdrawal and crating density in transit on metabolism and meat quality of broilers at slaughter weight

Commercial broilers are exposed to a number of stressors prior to slaughter, including feed deprivation, crating density (high vs. low), and transportation. Hence, the individual and additive or overruling effects of these stressors on welfare and energy metabolism were examined. Live weight gain, rectal temperature, physiological responses, and meat quality of broilers were determined. The fasting of broilers before being transported resulted in a decrease of triglycerides, uric acid, and triiodothyronine concentrations, indicating a negative energy balance. Feed withdrawal was also associated with a reduction in body weight, and highest body weight losses were observed after being fasted for 13 h. For some parameters there was a combined effect of feed withdrawal and crating density, whereas for others the crating density overruled the effect of previous feed withdrawal: broilers that had no access to feed before being transported had higher thyroxine and lower lactate concentrations (only at high crating density) compared with their fed counter-parts before the transport process, indicating the combined effect of both actions. The distinction due to the feeding pattern could no longer be observed for the plasma uric acid, nonesterified fatty acids, triglycerides, and triiodothyronine concentrations because it was overruled by the transport effect, especially if broilers were transported at high crating density. Plasma corticosterone concentrations increased as a consequence of the procedure of transportation and peaked if broilers were crated at high density. In our study, no significant effect of preslaughter stressors on meat quality, plasma creatine kinase activity, or lipid peroxidation levels were noticed. It can be concluded that transportation at high stocking densities should be avoided to reduce economic losses and stress to broilers. Plasma hormone as well as metabolites, rectal temperature, and heat shock protein 70 mRNA all indicated the high stress level of broilers. Furthermore, this effect often overruled the feed withdrawal and transport effect, indicating the importance of crating density.status: publishe

Further investigations on the role of diet-induced thermogenesis in the regulation of feed intake in chickens: Comparison of age-matched broiler versus layer cockerels

The aim of this study was to investigate the role of diet-induced thermogenesis (DIT) in the regulation of feed intake in age-matched broiler and layer cockerels. In addition, the effect of genotype on endocrine functioning and key metabolites of the intermediary metabolism as well as on the expression of muscular uncoupling protein (avUCP) was explored. One-day-old male broiler (Ross) and layer (ISA Brown) chicks were reared under standard conditions on commercial broiler starter and finisher diets. From 22 d of age, twice per week, 3 broiler and 6 layer cockerels were placed in open circuit respiratory chambers. After adaptation, the animals were feed-deprived for 24 h, and heat production was measured by indirect calorimetry. During the subsequent 7-h refeeding period, feed intake and DIT were measured. Blood samples were taken after feed deprivation and refeeding. Muscle samples were taken after refeeding for determination of avUCP expression. A significantly higher heat production per metabolic BW (MBW) in the layer compared with the broiler cockerels, independent of nutritional state, suggests that the broilers used a greater proportion of the metabolizable energy intake for growth. The DIT per MBW and per gram of feed intake was higher for the layer than for the broiler cockerels. However, feed intake per MBW was also significantly higher in the layer cockerels. Thus, no feedback effect of DIT on feed intake per MBW was observed, and the model formulated for adult mammals relating feed intake to DIT could not be corroborated. The muscular expression of avUCP was not different between genotypes, which does not support the hypothesis of an involvement of avUCP in the higher DIT measured in layer cockerels. Circulating uric acid, glucose, triglyceride, and free fatty acid levels were significantly elevated in the layer compared with the broiler cockerels. As the diet was formulated according to broiler requirements, the higher metabolite levels of the layer cockerels might reflect a relative oversupply of dietary nutrients.status: publishe

Rate of metabolic decarboxylation of leucine as assessed by a L[1-C-13(1)]leucine breath test combined with indirect calorimetry of broiler chickens fed isocaloric diets with different protein : fat ratio

Research has shown that broiler chickens reared on a low-protein diet have a more efficient protein digestion. However, information on the fate of absorbed amino acids in relation to the dietary crude protein level in poultry is sparse. Therefore, this study aimed at developing a methodology for a 1-C-13(1)-leucine breath test combined with indirect calorimetry, and to apply this technique using broiler diets known to induce differences in protein retention. From 14 days of age onwards, broiler chickens were reared on one of two isocaloric diets with substitutions between fat and protein [low-protein (LP) vs. high-protein (HP) diet: 130.4 vs. 269 g protein/kg; and 101.8 vs. 27.9 g fat/kg]. Every 4 or 5 days, three chickens per diet were placed in the respiratory cells for 48 h. The broilers were intubated with 40 mg 1-C-13(1)-leucine/kg body weight, followed by breath sampling for 4 h at 15-min intervals and mass spectrometric analysis of the C-13:C-12 ratio in the samples. The CO2 level in the respiratory cell air was monitored and excreta samples were collected. The methodology to study [1-C-13(1)]leucine decarboxyation in chickens using a breath test combined with indirect calorimetry was accomplished. Results of the nitrogen balance test indicated that the LP broilers had an improved dietary protein retention compared with the HP animals. Moreover, LP chickens decarboxylated a significantly lower percentage of [1-C-13(1)]leucine, demonstrating several 'protein- or amino acid-sparing' mechanisms in animals reared on a diet with lower protein level, both at the digestive and at the postabsorptive level.status: publishe

Gene expression, tissue distribution and potential physiological role of uncoupling protein in avian species

International audienc

The effect of the protein level in a pre-starter diet on the post-hatch performance and activation of ribosomal protein S6 kinase in muscle of neonatal broilers.

The cytoplasmic serine/threonine ribosomal protein S6 kinase (S6K1) plays a critical role in controlling protein translation. There is evidence that amino acids regulate S6K1 and protein synthesis in avian species, but the effect of dietary protein level on the activation of S6K1 in neonatal chicks is unknown. Therefore, the aim of the present experiment was to investigate the effect of different protein levels, supplied during the first 5 d post-hatch, on body growth, breast muscle development and on the activation of S6K1 and its downstream target, the S6, in neonatal chicks. Chicks were fed a pre-starter diet during the first 5 d post-hatch containing low (19.6 % crude protein (CP); LP), medium (23.1 % CP; MP) or high (26.7 % CP) levels (HP) of protein. Weight gain of chicks fed the HP diet was higher (P < 0.05) compared with those fed the LP diet during day (d)3-d5 and the numerical advantage of this group was maintained from d2 to d7. On d2 and d3, greater levels of S6K1 and S6 phosphorylation and/or activity were observed in chicks receiving the HP diet compared with LP and MP diets, without differences between results of the latter two dietary treatments. In conclusion, the present results suggest that early protein nutrition impacts the development of broiler chicks

Effects of dietary protein content and 2-hydroxy-4-methylthiobutanoic acid or DL-methionine supplementation on performance and oxidative status of broiler chickens.

Besides its typical role as an amino acid in protein synthesis, methionine is an important intermediate in methylation reactions. In addition, it can also be converted to cysteine and hence plays a role in the defence against oxidative stress. The present study was conducted to investigate further the role of DL-methionine (DLM) and its hydroxy analogue, DL-2-hydroxy-4-methylthiobutanoic acid (DL-HMTBA), on zootechnical performance and oxidative status of broiler chickens. Male broiler chickens were reared on two diets differing in crude protein (CP) content (low-protein, 18.3 % v. high-protein, 23.2 % CP) and were supplemented either with 0.25 % DLM or 0.25 % DL-HMTBA. Reducing the dietary protein content resulted in an impaired body weight gain (P < 0.0001). However, supplementation of DL-HMTBA to the low-protein diet partially alleviated these negative effects (P = 0.0003). This latter phenomenon could be explained by the fact that chickens fed DL-HMTBA-supplemented diets displayed a better antioxidant status as reflected in lower lipid peroxidation probably as a consequence of their higher hepatic concentrations of total and reduced glutathione compared with their DLM counterparts. On the other hand, within the high protein levels, uric acid might be an important antioxidant to explain the lower lipid peroxidation of high-protein DL-HMTBA-supplemented chickens. Hepatic methionine sulfoxide reductase-A gene expression was not significantly affected by the dietary treatments. In conclusion, the present study indicates that there are interactions between dietary protein content and supplementation of methionine analogues with respect to broiler performance and antioxidant status, also suggesting a causal link between these traits

Haemodynamic or metabolic stimulation tests to reveal the renal functional response: requiem or revival?

Renal stimulation tests document the dynamic response of the glomerular filtration rate (GFR) after a single or a combination of stimuli, such as an intravenous infusion of dopamine or amino acids or an oral protein meal. The increment of the GFR above the unstimulated state has formerly been called the renal functional reserve (RFR). Although the concept of a renal reserve capacity has not withstood scientific scrutiny, the literature documenting renal stimulation merits renewed interest. An absent or a blunted response of the GFR after a stimulus indicates lost or diseased nephrons. This information is valuable in preventing, diagnosing and prognosticating acute kidney injury and pregnancy-related renal events as well as chronic kidney disease. However, before renal function testing is universally practiced, some shortcomings must be addressed. First, a common nomenclature should be decided upon. The expression of RFR should be replaced by renal functional response. Second, a simple protocol must be developed and propagated. Third, we suggest designing prospective studies linking a defective stimulatory response to emergence of renal injury biomarkers, to histological or morphological renal abnormalities and to adverse renal outcomes in different renal syndromes.status: publishe