Alterations in the liver of intrauterine growth retarded piglets may predispose to development of insulin resistance and obesity in later life.

Intrauterine growth retardation (IUGR) leads to increased predisposition to metabolic syndrome in adult life but the mechanisms remain obscure. Considering a significant number of functional similarities, IUGR piglets appear to be a good model to study the development of this syndrome in humans. The aim of the present study was to investigate the ultrastructure and proteomic profile of the liver in IUGR pig neonates to discover early markers of predisposition to obesity and insulin resistance. In our study intestine and liver tissue samples were investigated in 7 day old IUGR and normal body weight (NBW) littermate piglets using histometry, mass spectrometry, in-tissue cytometry analysis and confocal microscopy. Compared to NBW, the liver in IUGR neonates was characterized by a significantly enhanced ratio of Kupffer cells to hepatocytes and insulin receptor abundance as well as higher percentages of cells expressing receptors for adipokines (resistin and adiponectin), increased expression of TNF-α (as marker of inflammation), and increased expression of insulin receptor and uncoupling protein 3 (UCP3). Moreover, NBW and IUGR differed in proteomic profile, including protein metabolism (proteasomes, cathepsin D, phermitin, phosphoglucomutase), carbohydrate metabolism (hexokinase 1, phosphoglucokinase, galactokinase, aldolase B, glucose-6-phosphate isomerase), oxidative stress and chromatin organization and DNA uptake (histones, lamin a/c). Reduction of hepatocyte numbers concomitant with significant modifications of expression of key hormones and enzymes for protein and carbohydrate metabolism in IUGR neonates may predispose to insulin resistance and obesity in adult life.

Mechanisms involved in the development of the small intestine mucosal layer in postnatal piglets.

The use of complementary visualization and measurement techniques allowed accurate description and quantification of changes in the intestinal mucosal architecture and provided a comprehensive outlook on the dynamics of remodelling and maturation processes of the mucosal layer taking place in the small intestine of piglets from birth to weaning. The aim of the study was to examine the early postnatal development of the small intestine in pigs. Three techniques were used: scanning electron microscopy (measurements of villus density and shape, height of enterocytes and microvilli, cell exfoliation, and location of extrusion zones), optical microscopy (cross section, measurement of structures: villus length and width; crypt depth; mucosal thickness), and confocal microscopy (cell localization, apoptosis, exfoliation and migration). The postnatal development of the mucosal layer of the small intestine was reflected in changes in the density, length, width, and shape of villi, crypt depth, replacement of enterocyte population, and arrangement. The presence of deep transverse furrows on villus corpus and vacuolated fetal-type enterocytes in the mucosal layer of the small intestine, which are able to engulf large amounts of colostrum shortly after birth, appears to play an important role in the observed phenomenon of straightening of the villus height and increasing of the villus diameter shortly after birth. We hypothesized that the intestinal mucosal layer is compressed before birth and ready to unfold within a short time after birth.

Invited review: Use of butyrate to promote gastrointestinal tract development in calves.

Promotion of microbial butyrate production in the reticulorumen is a widely used method for enhancing forestomach development in calves. Additional acceleration of gastrointestinal tract (GIT) development, both the forestomach and lower parts of the GIT (e.g., abomasum, intestine, and also pancreas), can be obtained by dietary butyrate supplementation. For this purpose, different sources (e.g., butyrate salts or butyrins), forms (e.g., protected or unprotected), methods (e.g., in liquid feed or solid feed), and periods (e.g., before or after weaning) of butyrate administration can be used. The aim of this paper was to summarize the knowledge in the field of butyrate supplementation in feeds for newborn calves in practical situations, and to suggest directions of future studies. It has been repeatedly shown that supplementation of unprotected salts of butyrate (primarily sodium salt) in milk replacer (MR) stimulates the rumen, small intestine, and pancreas development in calves, with a supplementation level equating to 0.3% of dry matter being sufficient to exert the desired effect on both GIT development and growth performance. On the other hand, the effect of unprotected butyrins and protected forms of butyrate supplementation in MR has not been extensively investigated, and few studies have documented the effect of butyrate addition into whole milk (WM), with those available focusing mainly on the growth performance of animals. Protected butyrate supplementation at a low level (0.3% of protected product in DM) in solid feed was shown to have a potential to enhance GIT development and performance of calves fed MR during the preweaning period. Justification of this form of butyrate supplementation in solid feed when calves are fed WM or after weaning needs to be documented. After weaning, inclusion of unprotected butyrate salts in solid feed was shown to increase solid feed intake, but the effect on GIT development and function has not been determined in detail, and optimal levels of supplementation are also difficult to recommend based on available reports. Future studies should focus on comparing different sources (e.g., salts vs. esters), forms (e.g., protected vs. unprotected), and doses of supplemental butyrate in liquid feeds and solid feeds and their effect not only on the development of rumen, abomasum, and small intestine but also the omasum and large intestine. Furthermore, the most effective source, form, and dose of supplemental butyrate in solid feed depending on the liquid feed program (e.g., MR or WM), stage of rearing (e.g., pre- or postweaning), and solid composition (e.g., lack or presence of forage in the diet) need to be determined.

Effect of butyrate infusion into the rumen on butyrate flow to the duodenum, selected gene expression in the duodenum epithelium, and nutrient digestion in sheep.

The aim of the study was to determine the effect of butyrate infusion into the rumen on butyrate flow to the duodenum, expression of short-chain fatty acid (SCFA) transporters (monocarboxylate transporter-1, -2, and -4) and receptors (G protein coupled receptor-41 and -43) in the duodenal epithelium and nutrient digestion in sheep. Eight wethers (39.0 ± 3.00 kg; mean ± SD) with ruminal and T-shape duodenal cannulas were allocated to 4 × 4 replicated Latin square design with each experimental period lasting for 21 d (12 d of adaptation and 9 d for data and sample collection). Experimental treatments were: 1) distilled water infusion into the rumen (CONT); 2) 15 g/d of butyric acid infusion into the rumen (BUT15); 3) 30 g/d of butyric acid infusion into the rumen (BUT30); and 4) 45 g/d of butyric acid infusion into the rumen (BUT45). The daily dose of butyrate was infused into the rumen via the rumen cannula, with 200 mL of solution of butyric acid and distilled water, at a constant rate (0.1389 mL/min) throughout the day using a peristaltic pump. Correspondingly, 200 mL/d of distilled water was infused into the rumen of CONT. The wethers were fed daily 900 g of chopped meadow hay and 200 g of concentrate in two equal meals at 0600 and 1800 h. Butyrate infusion into the rumen did not affect total SCFA concentration in the rumen fluid ( > 0.11). Molar proportion of butyrate in total SCFA linearly increased, and molar proportion of acetate and isovalerate linearly decreased ( ≤ 0.02) with an increasing amount of butyrate infused into the rumen. The molar proportion of butyrate in total SCFA in the duodenal digesta linearly increased ( < 0.01), and butyrate flow to duodenum tended to linearly increase ( = 0.06) with an increasing dose of exogenous butyrate delivered to the rumen. Butyrate infusion into the rumen did not affect ( ≥ 0.14) the mRNA expression of monocarboxylate transporter-2 and -4 and G protein coupled receptor-43 in the duodenal epithelium. The G protein coupled receptor-41 and monocarboxylate transporter-1 mRNA expression in the duodenal epithelium was very low in many of the analyzed samples. Digestibility of organic matter, neutral detergent fiber, and acid detergent fiber in the stomach (forestomach and abomasum) decreased for BUT15 and BUT30 and then increased for BUT45 (quadratic, ≤ 0.04); however, neither digestibility in the intestine nor total tract digestibility differed between treatments ( ≥ 0.10).

The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion.

Effect of microencapsulated sodium butyrate in the close-up diet on performance of dairy cows in the early lactation period.

Two trials were conducted to determine the effect of sodium butyrate microencapsulated within triglyceride matrix (Na-butyrate) in the close-up period on performance of dairy cows and rumen papillae development. In trial 1, 26 Holstein-Friesian cows were randomly allocated to 2 groups (13 cows/group) and fed prepartum a total mixed ration (TMR) without or with 300g of Na-butyrate/d from 30 d before expecting calving to parturition. After calving, the same lactational TMR without Na-butyrate was offered to both treatments. Dry matter intake and milk yield were monitored daily to 60 d in milk, and body condition of cows was scored on d 30, 21, and 4 before parturition and d 14, 31, and 60 after parturition. On d 15, 10, and 5 before parturition blood samples were collected from 6 cows randomly chosen from each group and analyzed for plasma ß-hydroxybutyrate and nonesterified fatty acids concentrations. No differences in dry matter (DM) intake, milk yield, body condition score, or plasma ß-hydroxybutyrate and nonesterified fatty acids concentrations was observed between treatments; however, in the last 5 d before parturition the cows receiving Na-butyrate ate 1.7kg of DM/d more, on average, as compared with control cows. In trial 2, 12 Holstein-Friesian growing bulls (404±48; body weight ± SD) were used to determine the effect of Na-butyrate inclusion in the diet on rumen papillae development. Bulls were randomly allocated to 2 groups (6 bulls/group) and fed TMR without or with 2% (on a dry matter basis) of Na-butyrate for 21 d. At the end of the study, bulls were killed and rumen fluid and rumen tissue samples from dorsal and ventral sac of the rumen were collected. No effect of Na-butyrate supplementation on BW of bulls and DMI during the trial period was observed. Sodium butyrate supplementation increased total short-chain fatty acid concentration in the rumen but had no effect on rumen pH, molar proportions of short-chain fatty acids, and NH3-N concentration. In dorsal sac of the rumen, papillae length and papillae cross-section surface area were increased as a result of Na-butyrate supplementation, whereas in the ventral sac a reverse effect was observed (significant treatment × location in the rumen interaction). Both in the dorsal and ventral sac of the rumen, dietary Na-butyrate increased rumen muscle layer thickness. Altogether, results of this study suggest that Na-butyrate supplementation in the close-up diet may have a potential to enhance rumen papillae growth and rumen adaptation to postpartum diet but lactation performance was not affected under conditions of the current study.

Differences in monocarboxylic acid transporter type 1 expression in rumen epithelium of newborn calves due to age and milk or milk replacer feeding.

The aim of the present study was to investigate whether besides age and solid feed intake, monocarboxylic acid transporter type 1 (MCT1) expression in the rumen epithelium of calves is affected by liquid feed type [whole milk (WM) or milk replacer (MR)]. Thirty bull calves at the mean age of 5 days were randomly allocated to five experimental groups (six calves/group). Six calves were slaughtered immediately after allocation to the trial (5 days of life), eighteen calves were fed MR and slaughtered at week intervals (on 12, 19, 26 days of life respectively), and six calves were fed WM and slaughtered at the 26 days of life. MCT1 protein abundance and the MCT1 mRNA level were investigated in the dorsal and ventral sack of the rumen. Solid feed intake and short-chain fatty acids (SCFA) concentration in the rumen fluid increased linearly with calves' age. The amount of the MCT1 protein and mRNA in the dorsal sac of rumen as well as the amount of MCT1 protein in the cranial ventral sac of rumen also increased linearly with calves' age. Calves fed WM had greater solid feed intake in the last week of the study as compared to calves fed MR, but SCFA concentration in the rumen fluid was not different. MCT1 mRNA expression in the cranial dorsal sac of rumen and protein MCT1 expression in both dorsal and ventral cranial sack of the rumen were higher in calves fed WM as compared to calves fed MR. This study confirmed age-dependent changes of MCT1 expression in the rumen epithelium of newborn calves and showed that its expression might be affected by liquid feed type.

Effect of method of delivery of sodium butyrate on maturation of the small intestine in newborn calves.

The effect of sodium butyrate (SB) supplementation in milk replacer (MR), starter mixture (SM), or both on small intestine maturation in newborn calves was investigated. Twenty-eight male calves with a mean age of 5 (± 1) d were randomly allocated into 1 of 4 groups (7 animals per group) and fed (1) MR and SM, without SB (MR(-) and SM(-), respectively; MR(-)/SM(-)); (2) MR(-) and SM supplemented with SB encapsulated within triglyceride matrix (SM(+), 0.6% as fed; MR(-)/SM(+)); (3) MR supplemented with crystalline SB (MR(+), 0.3% as fed) and SM(-) (MR(+)/SM(-)); or (4) MR(+) and SM(+) (MR(+)/SM(+)). The MR was offered in amounts equal to 10% of initial body weight of the calf. The SM was blended with whole corn grain (50/50; wt/wt) and offered ad libitum as a starter diet. Calves were slaughtered at 26 d (± 1) of age and small intestine development was investigated. Treatment with MR(+) decreased villus height in the proximal jejunum and decreased villus height, crypt depth, and tunica mucosa thickness in the middle jejunum, whereas treatment with SM(+) tended to increase small intestine weight and crypt depth in the proximal jejunum, and increased villus height in the distal jejunum. In the duodenum, crypt depth and tunica mucosa thickness were greater for the MR(-)/SM(+) group compared with MR(-)/SM(-), MR(+)/SM(-), and MR(+)/SM(+) groups. In the ileum, crypt depth was less for MR(-)/SM(+) compared with MR(-)/SM(-). Supplementation with SB in both MR and SM enhanced cell proliferation and decreased apoptosis in the middle jejunum mucosa. Regarding brush border enzyme activities, addition of SB to MR increased lactase activity in the middle jejunum and maltase activity in the distal jejunum, and tended to increase lactase activity in the distal jejunum, aminopeptidase A activity in the middle jejunum and ileum, and aminopeptidase N activity in the ileum. In contrast, SM(+) increased dipeptidylpeptidase IV activity in the distal jejunum and tended to increase aminopeptidase N in the distal jejunum. In conclusion, both MR(+) and SM(+) affected small intestine development in newborn calves. This effect depended on the method of SB delivery but MR(+) generally had a more pronounced effect. No synergistic effect of SB supplementation into MR and SM was found.

Early-effect of bariatric surgery (Scopinaro method) on intestinal hormones and adipokines in insulin resistant Wistar rat.

Bariatric surgery consists in duodenal exclusion from the food passage in obese patients with coexistent type 2 diabetes. Nowadays bariatric surgery is considered the most effective method of glycemic index normalization and insulin resistance reduction. Recent results on obese and non-obese rats showed remission of type 2 diabetes symptoms within few days after the surgery. The aim of the present work was to analyze the mechanisms of neuro-hormonal regulation responsible for early normalization of metabolic syndrome after bariatric surgery. In present study the concentration of selected intestinal hormones and adipokines in blood plasma and gastrointestinal tissues were analyzed. Study was conducted on Wistar rats. Animals were divided into three groups (each n=6): control (SH) shame-operated rats; animals in which visceral fat tissue was extracted (LP); and rats in which Scopinaro bariatric surgery was performed (BPD). Immunochemistry analysis of blood plasma showed decrease of insulin concentration in BPD and LP and increase of polypeptide YY (PYY) in BPD group as compared to the control. In duodenal mucosa homogenates the tendency to reduce insulin in LP and BPD group, and increase PYY and visfatin in BPD group was observed. Histometry analysis showed reduction of mucosa thickness in excluded segments of gastrointestinal tract in BPD group as compared to the SH and LP. Concluding, model studies on rats allowed better understanding of mechanisms important for early normalization of glycemic index and insulin resistance reduction in rats.

Influence of fundectomy and intraperitoneal or intragastric administration of apelin on apoptosis, mitosis, and DNA repair enzyme OGG1,2 expression in adult rats gastrointestinal tract and pancreas.

Apelin, endogenous ligand of G protein-coupled apelin receptor (APJ), is released into the gastrointestinal lumen, however, local effect of luminal apelin on gut epithelium has not been elucidated so far. The present study aimed to determine the effects of fundectomy, and intraperitoneal or intragastric administration of apelin on pancreatic, gastric and intestinal epithelium apoptosis, mitosis and DNA repair enzyme OGG1,2 expression in adult Wistar rats. Apelin-13 was given by intraperitoneal or gastric gavage twice a day for 10 days (100 nmol/kg b. wt./day). Fundectomized rats did not receive apelin. Control groups received saline as placebo. At the end of the experiment the rats were sacrificed and the pancreas, gastric fundus, duodenum, middle jejunum and colon tissue samples were harvested for immunofluorescence studies. Intraperitoneal and intragastric apelin-13 reduced apoptosis, mitosis and number of DNA damages in rats gastrointestinal tract (p≤0.001) as compared to control. In fundectomized rats, the apoptotic index in the pancreas and colon was decreased (p<0.001), and in the stomach and jejunum was increased (p<0.001). Mitotic index was decreased in all gastrointestinal tissues. Number of DNA damages (p≤0.001) in fundectomized rats was reduced except stomach where OGG1,2 expression was increased (p≤0.001) as compared to control. In conclusion, circulating and luminal exogenous apelin-13 caused similar effects on intestinal epithelium. Endogenous (gastric) apelin is important for renewal of intestinal epithelium in adult rats. Pharmacological doses of apelin-13 may reduce the cell turnover in the upper gastrointestinal tract epithelium and pancreas, and improve the overall gut health.

Does different approach during pancreatoduodenectomy influence intestinal migrating myoelectrical complex recovery? Study in experimental pig model.

It is said that leaving intact the functional motor unit of the pylorus leads to better gastric emptying and reduces postoperative upper gut motility disturbances. However, despite obvious different surgical approach, both major pancreatoduodenectomies lead to substantial myoelectrical dysfunctions. The latter are not efficiently recognized. We compared Whipple and Longmire-Traverso procedures in terms of electromyography patterns of the upper jejunum musculature and the density of Cajal cells network. Twelve male weaned pigs underwent surgery first to implant bipolar electrodes and telemetry transmitters for continuous electromyography recordings and then, after 1 week recovery, to create Whipple (n=6) and Longmire-Traverso (n=6) pancreatoduodenectomies. The first myoelectric activity was already registered 1-2 hours after both operations. Time to first regular patterns of migrating myoelectrical complex activity was significantly longer in the Whipple than in the Longmire-Traverso group (68.2±12.9 versus 27.8±51 hours, p=0.002). However, the restored patterns were substantially disturbed in both groups. Namely, after Longmire-Traverso operation, migrating myoelectrical complex cycles were very often and significantly shorter versus control ones, with reverse migration in the area of anastomosis while after Whipple procedure migrating myoelectrical complex cycles were less frequent and of short duration, significantly shorter in comparison even with Longmire-Traverso group. Cajal cells network in the vicinity of anastomosis, and distally from it, presented greater destruction after the Whipple operation. In conclusion, the advantage of one of two major pancreatoduodenectomies in terms of myoelectrical activity correctness in upper gut has not been proved in the study.

Structural and functional development of small intestine in intrauterine growth retarded porcine offspring born to gilts fed diets with differing protein ratios throughout pregnancy.

Protein level in the maternal diet plays a crucial role in fetal programming during pregnancy. Low or high protein level increases the risk of intrauterine growth retardation (IUGR). The aim of this study was to investigate the structural and functional development of the small intestine in piglets from sows fed a control (C, 12.1% protein), a high protein (HP, 30% protein), or a low protein (LP, 6.5% protein) diet during pregnancy. Newborns were classified as IUGR (birth weight ≤1.18 kg) and non-IUGR (birth weight >1.18 kg). The piglets were euthanized on postnatal day (PD)1, PD28 and PD188. The LP diet in non-IUGR neonates resulted in decreased body weight on PD1. The LP and HP diets resulted in both decreased body weight and delayed catch-up growth in the IUGR piglets. The HP and LP-diets increased the length of villi on PD1 in non-IUGRs but not in IUGRs. At birth, the expressions of Ki67 and active caspase 3 in mid-jejunum epithelium of HP and LP non-IUGR neonates were significantly lower as compared to C non-IUGRs whilst in IUGRs the respective expressions were as high as in C non-IUGRs. The postnatal dynamics of brush border enzyme activities and vacuolated enterocytes disappearance showed significant drop in enterocyte maturation in IUGR as compared to non-IUGR neonates. In conclusion, both HP and LP diets led to retarded development of non-IUGR piglets. In IUGR piglets both HP and LP diets resulted in delayed catch-up growth, without adaptive changes in brush border digestive enzymes.

The effect of exogenous apelin on the secretion of pancreatic juice in anaesthetized rats.

Apelin is known to stimulate cholecystokinin (CCK) and inhibit insulin release, however the mechanisms on pancreatic secretion remain unclear. The present study aimed to determine the expression of apelin and apelin receptor in the pancreas by immunofluorescence studies and the effect of exogenous apelin on the secretion of pancreatic juice in anesthetized rats. Pancreatic-biliary juice (P-BJ) was collected from Wistar rats treated with apelin (10, 20 and 50 nmol/kg b.w., boluses given every 30 min intravenously or intraduodenaly). The same apelin doses were administered to rats subjected to intraduodenal tarazapide, capsaicin or vagotomy. Pancreatic blood flow was measured by a laser doppler flowmeter. Direct effects of apelin were tested on dispersed acinar cells. Apelin receptor was expressed on acinar cells, pancreatic duct and islets cells, whereas apelin in pancreatic acini, but not in the islets. Intravenous apelin decreased P-BJ volume, protein and trypsin outputs in a dose-dependent manner. In contrast, intraduodenal apelin stimulated P-BJ secretion. Pharmacological block of mucosal CCK(1) receptor by tarazepide, vagotomy and capsaicin pretreatment abolished the effects of intravenous and intraduodenal apelin on P-BJ volume, protein and tryspin outputs. Apelin decreased the pancreatic blood flow. Apelin at 10(-6) M increased the release of amylase from non-stimulated and CCK-8-stimulated acinar cells. In conclusion, apelin can affect the exocrine pancreas through a complex mechanism involving local blood flow regulation and is driven by vagal nerves.

Effect of method of delivery of sodium butyrate on rumen development in newborn calves.

The effect of sodium butyrate (SB) supplementation in milk replacer (MR) or in starter mixture (SM) or in both MR and SM on performance, selected blood parameters, and rumen development in newborn calves was determined. Twenty-eight male calves with a mean age of 5 (±1) d were randomly allocated into 1 of 4 groups (7 animals per group) and fed (1) MR and SM, both without SB (MR(-) and SM(-), respectively); (2) MR(-) and SM supplemented with SB encapsulated within a triglyceride matrix (SM(+), 0.6% as fed; 30:70 butyrate-to-triglyceride matrix); (3) MR supplemented with crystalline SB (MR(+), 0.3% as fed) and SM(-); or (4) MR(+) and SM(+). The MR was offered in an amount equal to 10% of the initial body weight (BW) of each calf. The SM was blended with whole corn grain (50/50; wt/wt) and offered ad libitum as a starter diet (0.3% encapsulated-within-triglyceride matrix SB when SM(+) was fed) from the first day of the trial. Calves were slaughtered at d 21 of a trial (mean age 26±1 d). Addition of SB into MR (MR(+)) positively affected BW and average daily gain, tended to decrease the number of days with electrolyte therapies from d 0 to 7, and tended to positively affect fecal consistency from d 8 to 14 of the trial. Inclusion of SB into SM (SM(+)) increased starter diet intake from d 15 to 21, decreased the number of days with scours, and tended to decrease the number of days with electrolyte therapies in the whole trial period. Both MR(+) and SM(+) increased plasma glucose in the whole trial period and MR(+) increased total serum protein at d 14. The SM(+) increased plasma glucagon-like peptide-2 (GLP-2) concentration at d 7 of the trial when compared with the concentration at d 0. Both MR(+) and SM(+) increased reticulorumen weight and papillae length and width. Based on these results, it can be concluded that addition of SB in MR positively affected BW gain, health, and some metabolic intermediates of calves and it stimulated rumen development indirectly, whereas SB supplementation in SM stimulated rumen development directly. Addition of SB both in MR and SM could be recommended for rearing calves.

Is rumen development in newborn calves affected by different liquid feeds and small intestine development?

The objective of the study was to determine the effect of different liquid feeds on calf small intestine and rumen development. Twenty-one bull calves (5 ± 1 d old) were randomly allocated to 3 groups and fed whole milk (WM), milk replacer (MR; 22% CP and 17.5% fat), or MR supplemented with sodium butyrate (MR+SB; 0.3% as fed). Liquid feed dry matter intake was equal between treatments and amounted to 1% of BW at the beginning of the trial. Starter diet was offered ad libitum. Animals were slaughtered at 26 (± 1) d of age. Calves fed WM had higher average daily gain in the whole trial and higher starter diet dry matter intake between d 15 to 21 of the trial as compared with calves fed MR and MR+SB. Calves fed MR lost on average 1.4 kg of BW within first 14 d of the trial and their BW tended to be lower at d 7, 14, and 21 of the study as compared with calves fed MR+SB. The empty jejunum and ileum weight, crypt depth, mitotic index in the middle jejunum were higher, and apoptotic index tended to be lower in calves fed WM as compared with calves fed MR and MR+SB. Calves fed WM also had higher aminopeptidase N activity in the middle jejunum and tended to have higher maltase activity in the distal jejunum as compared with calves fed MR and MR+SB. The mitotic index was higher and apoptotic index was lower in the middle jejunum, and aminopeptidase A activity tended to be higher in the distal jejunum of calves fed MR+SB as compared with those fed MR. Calves fed WM had greater papillae length and width, and tended to have greater muscle layer thickness as compared with calves fed MR and MR+SB. Reticulorumen weight, reticulorumen weight expressed as percent of whole stomach weight, and papillae length and width were higher in calves fed MR+SB as compared with those fed MR. Additionally, calves fed WM had higher plasma glucose and urea in the whole trial period as compared with calves fed MR and MR+SB, and plasma glucose was higher in calves fed MR+SB as compared with those fed MR. Significant positive Pearson correlations were found between small intestine and reticulorumen weights as well as between activity of brush border lactase, maltase, aminopeptidase A, and aminopeptidase N and reticulorumen weight. Different liquid feeds affect small intestine development, animal growth, solid feed intake and metabolic status of calves and this effect can indirectly influence the development of forestomachs.

Pancreatic enzyme deficiency depends on dietary protein origin in milk-fed calves.

In young mammals, milk proteins and their substitutes are used in milk formula. Protein substitution modifies diet digestibility and pancreatic secretions. The aim of this study was to test if milk protein substitution could generate pancreatic deficiency in milk-fed calves. The effect of pancreatic juice on the digestibility of proteins was studied. Measurement of apparent fecal nutrient digestibility was used to estimate digestion. Ten calves (60 to 130 d old) were chronically fitted with pancreatic accessory duct cannulas and 2 duodenal cannulas to provide precise measurement, sampling, and reintroduction of pancreatic juice as well as additional infusions. Animals were fed milk formula based on skim milk powder or soybean concentrate. Level of deficiency depended on dietary protein origin. Twice as much protein or trypsin was required with a soybean concentrate diet than with a skim milk powder diet to obtain maximal nutrient digestibility. Pancreatic protein concentration in the juice can be used to differentiate between normal and deficient animals. Among these proteins, trypsin measurement is a good pancreatic deficiency marker. These results confirmed the major role of exocrine pancreatic secretions in producing optimal digestion in young calves. Furthermore, practical applications of these results can be applied for the young in other animal species and in humans.

Insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) mRNA levels in relation to the gastrointestinal tract (GIT) development in newborn calves.

The study was aimed at determining the age-depended changes in insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) mRNA levels in relation to the gastrointestinal tract (GIT) development in newborn calves. Twenty four male calves (5-day-old) were randomly allocated to 4 groups which were slaughtered at day 5, 12, 19 and 26 of their life, respectively. Tissue samples from the rumen, abomasum, duodenum, jejunum and liver were taken for analysis, and the level of IGF-1 and IGF-2 mRNA was determined using RT semi-quantitative PCR method. Both IGF-1 and IGF-2 mRNA level was the biggest on 5 day of life, significantly decreased up to day 12-19 in most of analyzed GIT parts, and started to increase thereafter. In the rumen the reduction in the amount of IGFs transcripts was associated with the reduction in papillae length and tunica muscularis thickness. The abomasum weight and tunica mucosa thickness increased from the 5 day up to 19 day of life, whereas abomasal IGF-1 mRNA level decreased together with calf's age up to 19 day of life, and the level of IGF-2 mRNA did not change. The reduction in IGFs mRNA level after 5 day of life in the duodenum (IGF-1 and IGF-2) and in the jejunum (IGF-1) was associated with reduction in villi length (duodenum and jejunum), and the increase of crypt depth (duodenum).

Dietary sodium butyrate supplementation increases digestibility and pancreatic secretion in young milk-fed calves.

The aim of this study was to test, in 8 calves fed milk formula based on soybean protein, the ability of sodium butyrate (SB) supplementation to improve nutrient digestibility and daily pancreatic secretions and to modify the kinetics of these secretions. Additionally, effects of duodenal SB infusion were evaluated. Plasma levels of gastrin, secretin, and cholecystokinin were measured. Butyrate supplementation in milk formula increased nutrient digestibility and total daily pancreatic secretions. For juice volume, this increase was most important from 12 to 17h after the morning meal. During the 3-h postprandial period, oral SB supplementation reduced the physiological decrease of postprandial pancreatic secretion (while duodenal digesta flow rate was maximal) and had a minor effect on plasma gut regulatory peptide concentrations. Compared with the diet without SB, ingestion of SB stimulated pancreatic secretion. Taken together, these results could explain the measured increase in nutrient digestibility. The data obtained after duodenal SB infusion did not indicate an effect on pancreatic secretion, apart from elevated lipase output compared with control. The mechanisms responsible for these events are not known and circulating gut regulatory peptides do not seem to be implicated. Our work brings new results regarding SB as a feed additive in young calf nutrition.

From the gut to the peripheral tissues: the multiple effects of butyrate.

Butyrate is a natural substance present in biological liquids and tissues. The present paper aims to give an update on the biological role of butyrate in mammals, when it is naturally produced by the gastrointestinal microbiota or orally ingested as a feed additive. Recent data concerning butyrate production delivery as well as absorption by the colonocytes are reported. Butyrate cannot be detected in the peripheral blood, which indicates fast metabolism in the gut wall and/or in the liver. In physiological conditions, the increase in performance in animals could be explained by the increased nutrient digestibility, the stimulation of the digestive enzyme secretions, a modification of intestinal luminal microbiota and an improvement of the epithelial integrity and defence systems. In the digestive tract, butyrate can act directly (upper gastrointestinal tract or hindgut) or indirectly (small intestine) on tissue development and repair. Direct trophic effects have been demonstrated mainly by cell proliferation studies, indicating a faster renewal of necrotic areas. Indirect actions of butyrate are believed to involve the hormono-neuro-immuno system. Butyrate has also been implicated in down-regulation of bacteria virulence, both by direct effects on virulence gene expression and by acting on cell proliferation of the host cells. In animal production, butyrate is a helpful feed additive, especially when ingested soon after birth, as it enhances performance and controls gut health disorders caused by bacterial pathogens. Such effects could be considered for new applications in human nutrition.

Adverse effects of nutritional programming during prenatal and early postnatal life, some aspects of regulation and potential prevention and treatments.

Nutritional programming, regulation and some ways for prevention/treatment to ameliorate or normalize adverse outcomes of programming are discussed. Epidemiological studies in human and animal experiments showed that nutrition during fetal and neonatal life may lead to related disorders in adulthood. But several argues may question its validity arising the question of the adequate models used to reproduce human situations. Protein level in milk formula intake by infant during neonatal life is discussed. Body weight at birth reflects the product growth trajectory during fetal life. Low birth weight is considered as the result of an adverse growth trajectory and is often associated with later metabolic diseases in adult age. But, the sum of prenatal growth trajectory, rapid growth in early infancy (catch up growth), early adiposity rebound in childhood must be considered to determine the origins of later diseases in adulthood. The review focuses the regulation of nutritional imprinting on hormonal and epigenetic mechanisms which are complementary. The HPA axis and GH-IGF axis may have a crucial role in the regulation induced by nutritional programming. The persistent alterations seem to be a consequence, at least in part, of elevated insulin levels during "critical periods" of pre- and early postnatal development. Also, leptin seems to play an important role in this complex system. New knowledge about these mechanisms involved suggest the development of new, rational, and effective preventive and/or therapeutic options before and/or after birth. Thus, early infancy may provide an opportunity for intervention aimed at reducing later disease risk.