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This review indicates that the energetic costs associated with the regulation of acid-base equilibrium in the dairy cow and the required adjustments with acidification (acidosis) are expected to be a considerable portion of the energy requirement of vital organs and the whole cow. This implies that acidosis at the rumen level, at the large intestinal level or at the metabolic level may have a significant impact on cow performance. Experimental research around the potentially negative effects of acidosis (particularly in the large intestine and metabolically) on cow functioning during early lactation is lacking however. There are indications for such negative effects and for the interaction between the occurrence of acidosis, the metabolic state of the dairy cow and impaired health which often occurs during this stage of lactation. Possible interactions between acidosis at the rumen, the large intestinal and the metabolic level are discussed. Influencing factors for acidosis in the rumen, the large intestine and metabolically are listed. An overview is given of features of the physiological state of a lactating cow during early lactation, of the metabolic phenomena that go together with the occurrence of acidosis at one of the three levels, and of the direct causal factors and processes involved with the development of such acidosis., Uit deze deskstudie blijkt dat de energetische kosten die gemoeid zijn met het reguleren van het zuur-base evenwicht in de melkkoe en het corrigeren van een verzuring (acidose) naar verwachting een aanzienlijk deel uitmaken van de energetische onderhoudsbehoefte van vitale organen en de gehele koe. Dit betekent dat acidose op pensniveau, dikke darmniveau of op het niveau van het metabolisme van de koe een belangrijke invloed kan hebben op het functioneren van de melkkoe. Er is nauwelijks experimenteel onderzoek beschikbaar rondom de mogelijk negatieve invloed van acidose (met name in de dikke darm en metabool) op het functioneren van de melkkoe tijdens de vroege lactatie. Er zijn aanwijzingen voor een dergelijke negatieve uitwerking en voor de interactie tussen het optreden van acidose, de metabole status van de melkkoe en de gezondheidsproblemen die dikwijls in deze periode optreden. Mogelijke interacties tussen acidose op het niveau van de pens, de dikke darm en het metabolisme worden bediscussieerd. Invloedfactoren bij een pensacidose, een dikke darmacidose en een metabole acidose worden opgesomd. Een overzicht wordt gegeven van de kenmerken van de fysiologische status van een melkkoe tijdens de vroege lactatie, van de metabole fenomenen die samengaan met het optreden van een acidose op een van de drie niveaus, en van de directe oorzakelijke factoren en processen die betrokken zijn bij het ontstaan van een acidose.

Introduction Intestinal chemosensory receptors and transporters are able to detect food-derived molecules and are involved in the modulation of gut hormone release. Gut hormones play an important role in the regulation of food intake and the control of gastrointestinal functioning. This mechanism is often referred to as “nutrient sensing”. Knowledge of the distribution of chemosensors along the intestinal tract is important to gain insight in nutrient detection and sensing, both pivotal processes for the regulation of food intake. However, most knowledge is derived from rodents, whereas studies in man and pig are limited, and cross-species comparisons are lacking. Aim To characterize and compare intestinal expression patterns of genes related to nutrient sensing in mice, pigs and humans. Methods Mucosal biopsy samples taken at six locations in human intestine (n = 40) were analyzed by qPCR. Intestinal scrapings from 14 locations in pigs (n = 6) and from 10 locations in mice (n = 4) were analyzed by qPCR and microarray, respectively. The gene expression of glucagon, cholecystokinin, peptide YY, glucagon-like peptide-1 receptor, taste receptor T1R3, sodium/glucose cotransporter, peptide transporter-1, GPR120, taste receptor T1R1, GPR119 and GPR93 was investigated. Partial least squares (PLS) modeling was used to compare the intestinal expression pattern between the three species. Results and conclusion The studied genes were found to display specific expression patterns along the intestinal tract. PLS analysis showed a high similarity between human, pig and mouse in the expression of genes related to nutrient sensing in the distal ileum, and between human and pig in the colon. The gene expression pattern was most deviating between the species in the proximal intestine. Our results give new insights in interspecies similarities and provide new leads for translational research and models aiming to modulate food intake processes in man.

Obesity and related diabetes are important health threatening multifactorial metabolic diseases and it has been suggested that 25% of all diabetic patients are unaware of their patho-physiological condition. Biomarkers for monitoring and control are available, but early stage predictive biomarkers enabling prevention of these diseases are still lacking. We used the pig as a model to study metabolic disease because humans and pigs share a multitude of metabolic similarities. Diabetes was chemically induced and control and diabetic pigs were either fed a high unsaturated fat (Mediterranean) diet or a high saturated fat/cholesterol/sugar (cafeteria) diet. Physiological parameters related to fat metabolism and diabetes were measured. Diabetic pigs' plasma proteome profiles differed more between the two diets than control pigs plasma proteome profiles. The expression levels of several proteins correlated well with (patho)physiological parameters related to the fat metabolism (cholesterol, VLDL, LDL, NEFA) and diabetes (Glucose) and to the diet fed to the animals. Studying only the control pigs as a model for metabolic syndrome when fed the two diets showed correlations to the same parameters but now more focused on insulin, glucose and abdominal fat depot parameters. We conclude that proteomic profiles can be used as a biomarker to identify pigs with developing metabolic syndrome (prediabetes) and diabetes when fed a cafeteria diet. It could be developed into a potential biomarkers for the early recognition of metabolic diseases.

The possible beneficial effects of surplus dietary Trp (+ 5 g Trp/kg diet) were investigated on factors related to stress, immunology, behavior, and N retention in post-weaning piglets (approximately 15 kg BW) challenged for 10 d with intravenous bacterial lipopolysaccharide (LPS; from Escherichia coli). Two diets fed restrictively (732 kJ NE/kg BW0.75/d) were compared: 1) basal diet (B; apparent ileal digestible Trp = 1.9 g/kg; a recommended level of Trp to warrant near-optimal growth in non-endotoxemic piglets) and 2) Trp enriched B (+ 5 g free L-Trp/kg) with 8 individually housed piglets per diet. Pooled salivary cortisol, but not plasma cortisol sampled at sacrifice, showed a tendency (P = 0.07) towards reduced concentrations in the Trp group (1.1 vs. 1.4 ng/mL; pooled SE = 0.1 ng/mL). Plasma C-reactive protein was reduced (P = 0.04) in the Trp group (0.9 vs. 5.0 mg/L; pooled SE = 1.3 mg/L), but haptoglobin, IL-6, tumor necrosis factor alpha, and LPS-induced fever were similar between the 2 dietary treatments. Physical activity related to approaching a human showed a tendency (P = 0.08) towards increased latency time in the Trp group (101 vs. 60 s; pooled SE = 16 s) but the times spent on standing, sitting, and lying were similar between dietary treatments. The ADFI, ADG (346 vs. 302 g/d; pooled SE = 14 g/d; P = 0.11), body N retention (11.6 vs. 11.0 g/d; pooled SE = 0.2 g/d; P = 0.18), and G:F (0.55 vs. 0.49; pooled SE = 0.03; P = 0.17) were not different between the Trp and B fed groups. In conclusion, surplus dietary Trp has limited impact on stress, immunology, behavior, and N retention in a pig model of systemic endotoxemia.

Background: Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet.Methods: Streptozotocin-diabetic pigs (~45 kg) were fed for 10 weeks supplemental (40% of dietary energy) saturated fat/cholesterol (SFC), unsaturated fat (UF) or starch (S) in an eucaloric dietary intervention study.Results: Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p < 0.01) in SFC compared to UF and S pigs. Fasting plasma NEFA concentrations (mmol/L) were highest (p < 0.05) in SFC (1.09 ± 0.17), intermediate in UF (0.80 ± 0.14) and lowest in S pigs (0.58 ± 0.14) whereas plasma glucose (~13 mmol/L), triglyceride (~0.5 mmol/L) and insulin (~24 pmol/L) concentrations were comparable among SFC, UF and S pigs. The postprandial response area under the curves (AUC, 0-4 h) for glucose but not for insulin and triglyceride responses were intermediate in SFC (617 ± 144) and lowest (p < 0.05) in UF (378 ± 157) compared to S pigs (925 ± 139). Fasting hepatic glucose production, hepatic and peripheral insulin sensitivity and blood pressure were not different among pigs. C-reactive protein (CRP) concentrations (mg/L) were highest (p < 0.05) in SFC (25 ± 4), intermediate in S (21 ± 3) and lowest in UF pigs (14 ± 2). Liver weights, liver and muscle triglyceride concentrations, and the surface area of aorta fatty streaks were highest (p < 0.01) in SFC pigs. A positive correlation between postprandial plasma CRP and aorta fatty streaks was observed in SFC pigs (R2= 0.95). Retroperitoneal fat depot weight (g) was intermediate in SFC (260 ± 72), lowest in S (135 ± 51) and highest (p < 0.05) in UF (571 ± 95) pigs.Conclusion: Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equall

Background The generation of energy from glucose is impaired in diabetes and can be compensated by other substrates like fatty acids (Randle cycle). Little information is available on amino acids (AA) as alternative energy-source in diabetes. To study the interaction between insulin-stimulated glucose and AA utilization in normal and diabetic subjects, intraportal hyperinsulinaemic euglycaemic euaminoacidaemic clamp studies were performed in normal (n = 8) and streptozotocin (120 mg/kg) induced diabetic (n = 7) pigs of ~40-45 kg. Results Diabetic vs normal pigs showed basal hyperglycaemia (19.0 ± 2.0 vs 4.7 ± 0.1 mmol/L, P <.001) and at the level of individual AA, basal concentrations of valine and histidine were increased (P <.05) whereas tyrosine, alanine, asparagine, glutamine, glutamate, glycine and serine were decreased (P <.05). During the clamp, diabetic vs normal pigs showed reduced insulin-stimulated glucose clearance (4.4 ± 1.6 vs 16.0 ± 3.0 mL/kg·min, P <.001) but increased AA clearance (166 ± 22 vs 110 ± 13 mL/kg· min, P <.05) at matched arterial euglycaemia (5-7 mmol/L) and euaminoacidaemia (2.8-3.5 mmol/L). The increase in AA clearance was mainly caused by an increase in non-essential AA clearance (93.6 ± 13.8 vs 46.6 ± 5.4 mL/kg·min, P <.01), in particular alanine (14.2 ± 2.4 vs 3.2 ± 0.4 mL/kg·min, P <.001). Essential AA clearance was largely unchanged (72.9 ± 8.5 vs 63.3 ± 8.5 mL/kg· min), however clearances of threonine (P <.05) and tyrosine (P <.01) were increased in diabetic vs normal pigs (8.1 ± 1.3 vs 5.2 ± 0.5, and 14.3 ± 2.5 vs 6.4 ± 0.7 mL/kg· min, respectively). Conclusions The ratio of insulin-stimulated glucose versus AA clearance was decreased 5.4-fold in diabetic pigs, which was caused by a 3.6-fold decrease in glucose clearance and a 2.0-fold increase in non-essential AA clearance. In parallel with the Randle concept (glucose - fatty acid cycle), the present data suggest the existence of a glucose and non-essential AA substrate interac

Background Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet. Methods Streptozotocin-diabetic pigs (~45 kg) were fed for 10 weeks supplemental (40% of dietary energy) saturated fat/cholesterol (SFC), unsaturated fat (UF) or starch (S) in an eucaloric dietary intervention study. Results Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p <0.01) in SFC compared to UF and S pigs. Fasting plasma NEFA concentrations (mmol/L) were highest (p <0.05) in SFC (1.09 ± 0.17), intermediate in UF (0.80 ± 0.14) and lowest in S pigs (0.58 ± 0.14) whereas plasma glucose (~13 mmol/L), triglyceride (~0.5 mmol/L) and insulin (~24 pmol/L) concentrations were comparable among SFC, UF and S pigs. The postprandial response area under the curves (AUC, 0-4 h) for glucose but not for insulin and triglyceride responses were intermediate in SFC (617 ± 144) and lowest (p <0.05) in UF (378 ± 157) compared to S pigs (925 ± 139). Fasting hepatic glucose production, hepatic and peripheral insulin sensitivity and blood pressure were not different among pigs. C-reactive protein (CRP) concentrations (mg/L) were highest (p <0.05) in SFC (25 ± 4), intermediate in S (21 ± 3) and lowest in UF pigs (14 ± 2). Liver weights, liver and muscle triglyceride concentrations, and the surface area of aorta fatty streaks were highest (p <0.01) in SFC pigs. A positive correlation between postprandial plasma CRP and aorta fatty streaks was observed in SFC pigs (R2 = 0.95). Retroperitoneal fat depot weight (g) was intermediate in SFC (260 ± 72), lowest in S (135 ± 51) and highest (p <0.05) in UF (571 ± 95) pigs. Conclusion Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high

Objectives The aim of this study was to compare the effects of single drug-eluting stents (DES) on porcine coronary function distal to the stent in vivo and in vitro. Background The mechanism of endothelial dysfunction occurring in human coronary conduit arteries up to 9 months after DES implantation is unknown. Methods A sirolimus-eluting stent (SES), paclitaxel-eluting stent (PES), and a bare-metal stent (BMS) were implanted in the 3 coronary arteries of 11 pigs. After 5 weeks, in vivo responses in distal coronary flow to different doses of bradykinin (BK) and nitrates were measured. In vitro, vasodilation to BK and nitrates, as well as vasoconstriction to endothelin (ET)-1 were assessed in both distal coronary conduit and small arteries. In addition, contributions of nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHFs) and cyclic guanosine monophosphate (cGMP) responses to BK-stimulation were determined in vitro. Results Both DES did not alter in vivo distal vasomotion. In vitro distal conduit and small arterial responses to BK were also unaltered; DES did not alter the BK-induced increase in cGMP. However, after NO synthase blockade, PES showed a reduced BK-response in distal small arteries as compared with BMS and SES (p <0.05). The ET-1–induced vasoconstriction and vascular smooth muscle cell function were unaltered. Conclusions In this study of single stenting in healthy porcine coronaries for 5 weeks, SES did not affect distal coronary vascular function, whereas PES altered distal endothelial function of small arteries under conditions of reduced NO bioavailability. Therefore, specifically the EDH-component of microvascular function seems affected by PES.

A rationale is given for a modelling approach to identify the mechanisms involved in the functioning and metabolic activity of tissues in the wall of the gastrointestinal tract. Maintenance and productive functions are discussed and related to the distinct compartments of the gastrointestinal tract and the metabolic costs involved. Functions identified are: tissue turnover; tissue proliferation; ion transport; nutrient transport; secretions of digestive enzymes, mucus and immunoglobulins; production of immune cells. The major nutrients involved include glucose, amino acids and volatile fatty acids. In vivo measurements of net portal fluxes of these nutrients in pigs and ruminants are evaluated to illustrate the complexity of physiology and metabolic activity of the gastrointestinal tract. Experimental evidence indicates that high, but variable and specific, nutrient costs are involved in the functioning of the gastrointestinal tract.