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Purpose: Nitrogen (N 2 ) is an indispensable metabolite required for the synthesis of protein. In animals, gut bacteria and, to a certain extent, even hepatocytes, are able to assimilate nitrogen from ammonium (NH 4 + ), which is essentially derived from the amine group (-NH 2 ) and which is at the same time a very toxic metabolite. Initially, NH 4 + is coupled to alpha-ketoglutarate (AKG), a reaction which results in the appearance of glutamate (one amine group), and after that, in the appearance of glutamine - containing two amine groups. The surplus of NH 4 + which is not utilized by AKG/glutamate/glutamine is eliminated as urea in the urine, via the urea cycle in hepatocytes. Plants bacteria also assimilate nitrogen from NH 4 + , by its fixation to ammonia (NH 3 )/NH 4 + ., Materials/methods: Previous studies have shown that AKG (also known as 2-oxo-glutaric acid or 2-oxopentanedioic acid), the primary metabolite of Rhizobium and gut bacteria, is essential for the assimilation of nitrogen., Results: Symbiotic bacteria produce AKG, which together with glutamate dehydrogenase (GDH), 'generates' primarily amine groups from NH 4 + . The final product is glutamate - the first amino acid. Glutamate has the capacity to be converted to glutamine, through the action of glutamine synthetase, after the assimilation of the second nitrogen from NH 4 + ., Conclusion: Glutamate/glutamine, derivatives of AKG metabolism, are capable of donating amine groups for the creation of other amino acids, following NH 2 transamination to certain metabolites e.g., short chain fatty acids (SCFA)., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Plasma levels of pancreatic and intestinal enzymes were measured after pancreatic duct ligation (PDL) to monitor pancreatic exocrine insufficiency (PEI) in a model using young pigs., Material/methods: Five, 6 week-old pigs (10.9±0.2kg), underwent PDL while age-matched, un-operated pigs were used as controls. Plasma levels of immunoreactive cationic trypsinogen (IRCT), amylase, lipase, and diamine oxidase (DAO) activities were analyzed for 48 days after PDL, including 1 week of oral pancreatic enzyme supplementation (PES) with Creon(®)., Results: PDL resulted in an arrested body growth and a rapid surge of pancreatic enzymes (IRCT, amylase and lipase) into the plasma. Nine days after PDL, the plasma levels of these pancreatic enzymes had decreased. IRCT then remained below the level in un-operated pigs while amylase only fell below control at 25 days. The intestinally derived marker DAO and plasma protein levels were unaffected by PDL but DAO decreased slightly with time in PEI pigs. One-week of oral PES restored body growth, but had little effect on pancreatic enzyme plasma levels, except for a tendency towards increased DAO., Conclusions: The study showed that PEI developed within 1-2 weeks after PDL and that only IRCT is a reliable plasma enzyme marker for this. The reduced plasma DAO indicated that PEI also affected the intestines, while PES therapy restored growth of the PDL pigs and slightly increased plasma DAO, suggesting an improved intestinal function., (Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background & Aims: Dietary chloroplast thylakoids have previously been found to reduce food intake and body weight in animal models, and to change metabolic profiles in humans in mixed-food meal studies. The aim of this study was to investigate the modulatory effects of thylakoids on glucose metabolism and appetite-regulating hormones during an oral glucose tolerance test in pigs fed a high fat diet., Methods: Six pigs were fed a high fat diet (36 energy% fat) for one month before oral glucose tolerance test (1 g/kg d-glucose) was performed. The experiment was designed as a cross-over study, either with or without addition of 0.5 g/kg body weight of thylakoid powder., Results: The supplementation of thylakoids to the oral glucose tolerance test resulted in decreased blood glucose concentrations during the first hour, increased plasma cholecystokinin concentrations during the first two hours, and decreased late postprandial secretion of ghrelin., Conclusion: Dietary thylakoids may be a novel agent in reducing the glycaemic responses to high carbohydrate and high glycaemic index foods. Thylakoids may in the future be promising for treatment and prevention of diabetes, overweight and obesity., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Exocrine pancreatic insufficiency (EPI) induced in young pigs by pancreatic duct ligation (PDL) early after weaning result in total growth deprivation while it has little effect in somewhat older pigs. The main objective was to study effects of EPI on gut structure and function in littermate pigs underwent to PDL at different age., Material/methods: Pigs, duct-ligated at either 7 (2 weeks post-weaning, PDL-7) or 16 weeks of age (PDL-16), and euthanized at an age of 21-23 weeks together with un-operated littermates were studied. The intestinal in vitro permeability was studied in separate PDL-pigs and compared to un-operated., Results: Morphometric analysis showed gut mucosal atrophy in the PDL-7 as compared to PDL-16 pigs, while no differences in mucosal disaccharidase activities. The intestinal permeability for different-sized markers was significantly increased in the PDL-pigs compared to the un-operated controls. Analyses of the intestinal digesta showed a total lack of pancreatic enzymes in all PDL-pigs, while instead new, as yet unidentified, enzyme-activities appeared., Conclusions: All EPI-pigs, independent of age at PDL-operation, displayed adaptive gut changes, however the EPI-pigs operated early after weaning appeared more sensitive, probably related to their gut maturity and possibly explaining the growth arrest seen in these pigs., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background & Aims: Young individuals with exocrine pancreatic insufficiency (EPI) show growth reduction that can be reversed by dietary pancreatic enzyme supplementation. Here we investigated whether feeding an elemental diet could replace the growth-promoting effect of enzyme supplementation in EPI pigs., Methods: Weaned pigs with intact pancreas (control) or pancreatic duct-ligated (EPI pigs) were given a commercial pig feed, a fat-enriched diet, or an elemental diet, intragastrically and intravenously, with or without porcine pancreatin (Creon) supplementation for 1 week., Results: Control pigs, irrespective of receiving pig feed or an elemental diet, increased their body weight by 13.4-20.1%, while EPI pigs showed negligible weight gain. Giving a fat-enriched diet did not improve growth of the EPI pigs. However, if the EPI pigs were supplemented with pancreatin in combination with fat-enriched feed or the elemental diet, i.v., their body weight increased by 16.6 %and 8.5%, respectively., Conclusion: Control pigs maintained normal growth, independently of the diet being given in polymeric or elemental form, while EPI pigs showed impaired growth when receiving the same diets without enzyme supplementation. Pancreatic juice and enzyme preparations, in addition to their digestive properties, also appear to affect nutrient assimilation and anabolism in young individuals.

Our results in a previous study indicated that the portal absorption of intragastrically fed alpha-ketoglutarate (AKG) was limited in young pigs. Our aim was to quantify the net portal absorption, first-pass metabolism, and whole-body flux of enterally infused AKG. In study 1, we quantified the net portal nutrient absorption in young pigs (n = 9) given an intraduodenal infusion of milk replacer [10 mL/(kg . h)] and either saline (control) or 930 micromol/(kg . h) AKG for 4 h. In study 2, we quantified the luminal disappearance of a duodenal AKG bolus in young pigs (n = 7). In study 3, we quantified the whole-body kinetics of (13)C-AKG metabolism when infused either enterally (n = 9) or intravenously (n = 9) in young pigs. In study 1, when compared with the control group, enteral AKG infusion increased (P < 0.01) the arterial (13.8 +/- 1.7 vs. 27.4 +/- 3.6 micromol/L) and portal (22.0 +/- 1.4 vs. 64.6 +/- 5.9 micromol/L) AKG concentrations and the net portal absorption of AKG [19.7 +/- 2.8 vs. 95.2 +/- 12.0 micromol/(kg . h)]. The mean fractional portal appearance of enterally infused AKG was 10.23 +/- 1.3%. In study 2, the luminal disappearance of AKG was 663 micromol/(kg . h), representing 63% of the intraduodenal dose. In study 3, the whole-body (13)C-AKG flux [4685 +/- 666 vs. 801 +/- 67 micromol/(kg . h)] was higher (P < 0.05) when given enterally than intravenously, but (13)CO(2) recovery was not different (37.3 +/- 1.0 vs. 36.2 +/- 0.7%dose). The first-pass splanchnic (13)C-AKG utilization was approximately 80%, of which 30% was oxidized to (13)CO(2). We conclude that the intestinal absorption of AKG is limited in young pigs largely due to substantial first-pass gastrointestinal metabolism.

Background and Aims: alpha-Ketoglutarate (AKG) has been suggested to play a particular role as an oxidative fuel for the gut, and thus may have a sparing function for fuels such as glutamate and aspartate. Using the pig model we aimed to quantify how the route of administration (intravenous, i.v.; intragastric, i.g.; intraduodenal, i.d.) affects AKG utilization, whole body energy expenditure (EE) and nutrient oxidation., Methods: Pigs (15 kg) were supplied with a complete nutrient solution (NS) via catheters. To explore the metabolic effects of AKG, 1.0 g AKG kgBW(-1)d(-1) was infused simultaneously with the NS using either the i.d., i.v. or i.g. route. [1-(13)C]AKG (15 mg kgBW(-1)) was infused i.d., i.v. or i.g., respectively, for 3h. AKG utilization (AKG UTIL) was estimated as AKG UTIL=100-(13)C recovery (% of (13)C dose). (13)C recovery was calculated from the (13)C enrichment in breath CO(2) and the whole-body CO(2) production., Results: AKG infusion and NS via the i.d. route resulted in a reduced AKG UTIL (40.1+/-6.7) as compared to the i.v. route (62.9+/-2.4, P<0.001) and i.g. route (62.3+/-1.6, P<0.001). The total EE was lower with the i.d. route of AKG and NS (745+/-68 kJkgBW(-0.62)d(-1)) as compared to the i.v. route (965+/-54 kJkgBW(-0.62)d(-1), P<0.005) and i.g. route (918+/-43 kJkgBW(-0.62)d(-1), P<0.005). Carbohydrate oxidation was increased with the i.d. route (38.2g+/-3.4 kgBW(-0.62)d(-1)) as compared to the i.v. route (27.8+/-2.9 gkgBW(-0.62)d(-1), P<0.08) and i.g. route (23.9+/-8.5 gkgBW(-0.62)d(-1), P<0.05). Fat oxidation was decreased (2.1+/-1.9 gkgBW(-0.62)d(-1); P<0.001) with the i.d. route as compared to the i.v. route (11.5+/-1.4 gkgBW(-0.62)d(-1), P<0.001) and i.g. route (11.9+/-3.1 gkgBW(-0.62)d(-1), P<0.001)., Conclusions: The i.d. infusion of AKG in combination with the NS affected the whole body EE and nutrient oxidation, in comparison to that obtained with the i.v. and i.g. routes. It was concluded that the i.d. administration of AKG markedly controlled the nutrient partitioning in the oxidation processes. Finally, in contrary to the observations with glutamine or glutamate, a considerable percentage of the AKG infusion was retained in the body irrespective of the route of administration.

Our aim was to quantify the intestinal metabolic fate of dietary alpha-ketoglutarate (AKG). Female pigs (n = 6; 21 d old) were implanted with arterial, venous, portal and gastric catheters and an ultrasonic portal flow probe and fed a corn and soybean meal-based diet. On the day of the experiment, the pigs received a 4-h intragastric infusion of sodium AKG at a rate equivalent to 0, 2.5, 5 or 10% of dietary intake. The net portal AKG balance of the control and 2.5% treatments did not differ and were not different from zero. However, the net portal AKG balance of both the 5 [163 micro mol/(kg. h)] and 10% [159 micro mol/(kg. h)] treatments were greater (P < 0.05) than the control. Despite significant net AKG absorption at the 5 and 10% levels, the net portal appearance represented only 10.8 and 6.7%, respectively, of the enteral input. The net portal appearances of glutamate, glutamine, ammonia and the branched-chain amino acids were not affected by dietary AKG level. We conclude that the absorption of dietary AKG is limited in young pigs and does not change the net portal balance of amino acids or ammonia.