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Dive into the research topics where Sietse Jan Koopmans is active.

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Featured researches published by Sietse Jan Koopmans.


Physiology & Behavior | 2005

Surplus dietary tryptophan reduces plasma cortisol and noradrenaline concentrations and enhances recovery after social stress in pigs

Sietse Jan Koopmans; Marko Ruis; R.A. Dekker; Hans van Diepen; Mechiel Korte; Zdzislaw Mroz

Social stress occurs in intensive pig farming due to aggressive behavior. This stress may be reduced at elevated dietary levels of tryptophan (TRP). In this study, we compared the effects of high (13.2%) vs. normal (3.4%) dietary TRP to large neutral amino acid (LNAA) ratios on behavior and stress hormones in catheterized pigs ( approximately 50 kg BW), which were exposed to social stress by placing them twice into the territory of a dominant pig ( approximately 60 kg) for 15 min. Pre-stress plasma TRP concentrations were 156+/-15 vs. 53+/-6 micromol/l (p<0.01) in pigs on the high vs. normal TRP diets, respectively. Pre-stress plasma cortisol and noradrenaline concentrations were twofold (p<0.01) and 1.4-fold (p<0.05) lower but plasma adrenaline concentration was similar in pigs on the high vs. normal TRP diets, respectively. During the social confrontations, pigs on the high vs. normal TRP diets show a tendency towards reduced active avoidance behavior (3.2+/-1.1 vs. 6.7+/-1.2 min, p<0.1) but their physical activity (8.5+/-0.6 vs. 10.2+/-0.8 min) and aggressive attitude towards the dominant pig (11+/-3 vs. 7+/-2 times biting) were similar. Immediate (+5 min) post-stress plasma cortisol, noradrenaline and adrenaline responses were similar among dietary groups. After the social confrontations, the post-stress plasma cortisol, noradrenaline and adrenaline concentrations and/or curves (from +5 min to 2 h) were lower/steeper (p<0.05) in pigs on the high vs. normal TRP diets. In summary, surplus TRP in diets for pigs (1) does not significantly affect behavior when exposed to social stress, (2) reduces basal plasma cortisol and noradrenaline concentrations, (3) does not affect the immediate hormonal response to stress, and (4) reduces the long-term hormonal response to stress. In general, pigs receiving high dietary TRP were found to be less affected by stress.


European Journal of Pharmacology | 2015

Considerations on pig models for appetite, metabolic syndrome and obese type 2 diabetes: From food intake to metabolic disease.

Sietse Jan Koopmans; T. Schuurman

(Mini)pigs have proven to be a valuable animal model in nutritional, metabolic and cardiovascular research and in some other biomedical research areas (toxicology, neurobiology). The large resemblance of (neuro)anatomy, the gastro-intestinal tract, body size, body composition, and the omnivorous food choice and appetite of the pig are additional reasons to select this large animal species for (preclinical) nutritional and pharmacological studies. Both humans and pigs are prone to the development of obesity and related cardiovascular diseases such as hypertension and atherosclerosis. Bad cholesterol (LDL) is high and good cholesterol (HDL) is low in pigs, like in humans. Disease-relevant pig models fill the gap between rodent models and primate species including humans. Diet-induced obese pigs show a phenotype related to the metabolic syndrome including high amounts of visceral fat, fatty organs, insulin resistance and high blood pressure. However, overt hyperglycaemia does not develop within 6 months after initiation of high sugar-fat feeding. Therefore, to accelerate the induction of obese type 2 diabetes, obese pigs can be titrated with streptozotocin, a chemical agent which selectively damages the insulin-producing pancreatic beta-cells. However, insulin is required to maintain obesity. With proper titration of streptozotocin, insulin secretion can be restrained at such a level that hyperglycaemia will be induced but lipolysis is still inhibited due to the fact that inhibition of lipolysis is more sensitive to insulin compared to stimulation of glucose uptake. This strategy may lead to a stable hyperglycaemic, non-ketotic obese pig model which remains anabolic with time without the necessity of exogenous insulin treatment.


Cardiovascular Diabetology | 2011

Dietary saturated fat/cholesterol, but not unsaturated fat or starch, induces C-reactive protein associated early atherosclerosis and ectopic fat deposition in diabetic pigs

Sietse Jan Koopmans; R.A. Dekker; Mariëtte T. Ackermans; Hans P. Sauerwein; Mireille J. Serlie; Heleen M.M. van Beusekom; Mieke van den Heuvel; Wim J. van der Giessen

BackgroundDiabetes 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.MethodsStreptozotocin-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.ResultsFasting 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.ConclusionDietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high dietary unsaturated fat load does not induce these abnormalities and shows beneficial effects on postprandial glycaemia in diabetic pigs.


Physiology & Behavior | 2009

Surplus dietary tryptophan inhibits stress hormone kinetics and induces insulin resistance in pigs

Sietse Jan Koopmans; Marko Ruis; R.A. Dekker; Mechiel Korte

Recently we have shown that surplus dietary tryptophan (TRP) reduced the plasma concentrations of cortisol and noradrenaline in pigs. Stress hormones are known to affect insulin sensitivity and metabolism. We now investigated the long-term effects of surplus dietary TRP on 1) plasma and urinary stress hormone kinetics, 2) insulin sensitivity for glucose and amino acid clearance, and 3) whole body nitrogen balance. Pigs were fed for 3weeks a high (13.2%) vs normal (3.4%) TRP to large neutral amino acids (LNAA) diet, leading to reduced fasting (14 h) plasma cortisol (17.1+/-3.0 vs 28.9+/-4.3 ng/mL, p<0.05) and noradrenaline (138+/-14 vs 225+/-21 pg/mL, p<0.005) concentrations, lower daily urinary noradrenaline (313+/-32 vs 674+/-102 ng/kg day, p<0.001) and adrenaline (124+/-13 vs 297+/-42 ng/kg day, p<0.001) but higher dopamine (5.8+/-0.5 vs 1.5+/-0.2 microg/kg day, p<0.001) excretions, respectively. Insulin sensitivities for both glucose and amino acid clearance, (as measured by the intraportal hyperinsulinaemic (1 mU/kg min) euglycaemic euaminoacidaemic clamp technique), were lower by 22% in pigs on the high vs normal TRP/LNAA diet (14.8+/-1.4 vs 18.9+/-0.9, p<0.05 and 69.7+/-4.3 vs 89.7+/-6.8 mL/kg min, p<0.05, respectively) without affecting urinary nitrogen excretion (35.5+/-1.0 vs 36.6+/-1.0% of dietary nitrogen intake, p=ns). In conclusion, long-term feeding of surplus dietary TRP inhibits both baseline adrenocortical and sympathetic nervous system activity, it induces insulin resistance for both glucose and amino acid clearance but it does not affect whole body protein catabolism. This indicates that the bioactive amino acid TRP contributes to homeostasis in neuroendocrinology and insulin action and that low baseline adrenocortical and sympatho-adrenal axis activity are associated with insulin resistance.


Jacc-cardiovascular Interventions | 2010

Specific coronary drug-eluting stents interfere with distal microvascular function after single stent implantation in pigs.

Mieke van den Heuvel; Oana Sorop; Wendy W. Batenburg; Charlotte L. Bakker; René de Vries; Sietse Jan Koopmans; Heleen M.M. van Beusekom; Dirk J. Duncker; A.H. Jan Danser; Willem van der Giessen

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 EDHF component of microvascular function seems affected by PES.


Journal of Animal Science | 2012

Effects of a simple or a complex starter microbiota on intestinal microbiota composition in caesarean derived piglets.

A.J.M. Jansman; Jing Zhang; Sietse Jan Koopmans; R.A. Dekker; Hauke Smidt

The present study was designed to develop a model in piglets that allows the investigation of the effects of postnatal association with a simple or a complex microbiota on gut health and development. Thirty piglets from 2 sows were obtained by caesarean delivery (day 0) and were equally divided over 2 treatment groups housed in separate clean, nonsterile rooms. All piglets received orally a simple microbiota consisting of Lactobacillus amylovorus, Clostridium glycolicum, and Parabacteroides spp. on days 1, 2, and 3 after birth. On day 3 and 4 the piglets received either a complex microbiota by providing them with a fecal inoculant of an adult sow [complex association (CA)] or a placebo inoculant [simple association (SA)]. Fecal microbiota composition, as determined by denaturing gradient gel electrophoresis and by pig intestinal tract chip (PITChip) analysis of 16S rRNA genes (days 3, 5, 7, 14, and 28), was less diverse in the SA group compared to the CA group. A difference in fecal microbiota composition between treatments persisted until the end of the study. It was concluded that the composition of microbiota in feces of cesarean delivery-derived piglets is influenced by bacterial association in the first days after birth. Differences in fecal microbiota composition between piglets exposed to a simple or complex inoculum at early age persisted for at least 3 wk.


BMC Biochemistry | 2011

The existence of an insulin-stimulated glucose and non-essential but not essential amino acid substrate interaction in diabetic pigs

Sietse Jan Koopmans; Jan VanderMeulen; Jan Wijdenes; Henk Corbijn; R.A. Dekker

BackgroundThe 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.ResultsDiabetic 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).ConclusionsThe 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 interaction in diabetic pigs whereby reduced insulin-stimulated glucose clearance seems to be partly compensated by an increase in non-essential AA clearance whereas essential AA are preferentially spared from an increase in clearance.


American Journal of Physiology-heart and Circulatory Physiology | 2016

Coronary microvascular dysfunction after long-term diabetes and hypercholesterolemia

Oana Sorop; Mieke van den Heuvel; Nienke S. van Ditzhuijzen; Vincent J. de Beer; Ilkka Heinonen; Richard van Duin; Zhichao Zhou; Sietse Jan Koopmans; Daphne Merkus; Wim J. van der Giessen; A.H. Jan Danser; Dirk J. Duncker

Coronary microvascular dysfunction (CMD) has been proposed as an important component of diabetes mellitus (DM)- and hypercholesterolemia-associated coronary artery disease (CAD). Previously we observed that 2.5 mo of DM and high-fat diet (HFD) in swine blunted bradykinin (BK)-induced vasodilation and attenuated endothelin (ET)-1-mediated vasoconstriction. Here we studied the progression of CMD after 15 mo in the same animal model of CAD. Ten male swine were fed a HFD in the absence (HFD, n = 5) or presence of streptozotocin-induced DM (DM + HFD, n = 5). Responses of small (∼300-μm-diameter) coronary arteries to BK, ET-1, and the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine were examined in vitro and compared with those of healthy (Normal) swine (n = 12). Blood glucose was elevated in DM + HFD (17.6 ± 4.5 mmol/l) compared with HFD (5.1 ± 0.4 mmol/l) and Normal (5.8 ± 0.6 mmol/l) swine, while cholesterol was markedly elevated in DM + HFD (16.8 ± 1.7 mmol/l) and HFD (18.1 ± 2.6 mmol/l) compared with Normal (2.1 ± 0.2 mmol/l) swine (all P < 0.05). Small coronary arteries showed early atherosclerotic plaques in HFD and DM + HFD swine. Surprisingly, DM + HFD and HFD swine maintained BK responsiveness compared with Normal swine due to an increase in NO availability relative to endothelium-derived hyperpolarizing factors. However, ET-1 responsiveness was greater in HFD and DM + HFD than Normal swine (both P < 0.05), resulting mainly from ETB receptor-mediated vasoconstriction. Moreover, the calculated vascular stiffness coefficient was higher in DM + HFD and HFD than Normal swine (both P < 0.05). In conclusion, 15 mo of DM + HFD, as well as HFD alone, resulted in CMD. Although the overall vasodilation to BK was unperturbed, the relative contributions of NO and endothelium-derived hyperpolarizing factor pathways were altered. Moreover, the vasoconstrictor response to ET-1 was enhanced, involving the ETB receptors. In conjunction with our previous study, these findings highlight the time dependence of the phenotype of CMD.


Journal of animal science and biotechnology | 2017

The effects of starter microbiota and the early life feeding of medium chain triglycerides on the gastric transcriptome profile of 2- or 3-week-old cesarean delivered piglets

P. Trevisi; D. Priori; Vincenzo Motta; Diana Luise; A.J.M. Jansman; Sietse Jan Koopmans; Paolo Bosi

BackgroundThe stomach is an underestimated key interface between the ingesta and the digestive system, affecting the digestion and playing an important role in several endocrine functions. The quality of starter microbiota and the early life feeding of medium chain triglycerides may affect porcine gastric maturation. Two trials (T1, T2) were carried out on 12 and 24 cesarean-delivered piglets (birth, d0), divided over two microbiota treatments, but slaughtered and sampled at two or three weeks of age, respectively. All piglets were fed orally: sow serum (T1) or pasteurized sow colostrum (T2) on d0; simple starter microbiota (Lactobacillus amylovorus, Clostridium glycolicum and Parabacteroides spp.) (d1-d3); complex microbiota inoculum (sow diluted feces, CA) or a placebo (simple association, SA) (d3-d4) and milk replacer ad libitum (d0-d4). The The T1 piglets and half of the T2 piglets were then fed a moist diet (CTRL); the remaining half of the T2 piglets were fed the CTRL diet fortified with medium chain triglycerides and 7% coconut oil (MCT). Total mRNA from the oxyntic mucosa was analyzed using Affymetrix©Porcine Gene array strips. Exploratory functional analysis of the resulting values was carried out using Gene Set Enrichment Analysis.ResultsComplex microbiota upregulated 11 gene sets in piglets of each age group vs. SA. Of these sets, 6 were upregulated at both ages, including the set of gene markers of oxyntic mucosa. In comparison with the piglets receiving SA, the CA enriched the genes in the sets related to interferon response when the CTRL diet was given while the same sets were impoverished by CA with the MCT diet.ConclusionsEarly colonization with a complex starter microbiota promoted the functional maturation of the oxyntic mucosa in an age-dependent manner. The dietary fatty acid source may have affected the recruitment and the maturation of the immune cells, particularly when the piglets were early associated with a simplified starter microbiota.


Proceedings of the Nutrition Society | 2014

Microbiota diversity during neonatal colonization impacts gut physiology in a pig model

Jean-Paul Lallès; A. Bizon; A. Taekema; Marie-Edith Arnal; Cr Stokes; Mick Bailey; Hauke Smidt; A.J.M. Jansman; Sietse Jan Koopmans

Reduced gut microbiota diversity is suspected to be detrimental in a variety of diseases, including inflammatory bowel diseases. Variation in microbiota composition during gut colonization is known to influence neonatal mortality and may be a risk factor for various non-infectious diseases such as allergy, metabolic disorders and obesity later in life. How neonatal microbiota diversity can modulate gut barrier function and defense systems is poorly understood. Therefore, the aim of the present study was to test the hypothesis that a complex microbiota is more suitable neonatally than a simplified microbiota for homeostatic development of gut function. This hypothesis was tested in a neonatal pig model (Lelystad ethics protocol No. 2011097). Piglets were delivered by Caesarean section and were kept in SPF facilities. They were then administered orally at day 2 and 3 a simple microbiota (SM, n=6) alone or with a faecal bacterial suspension from an unrelated sow at day 4 (CM, n=6). The three bacterial genera and strains of the SM mixture (‘Bristol mix’) were recently shown to reliably colonize the gut of germfree pigs. The piglets were slaughtered at 16 days of age. Segments of proximal jejunum, distal ileum and proximal colon and plasma were collected. Gut samples were analysed for villus-crypt morphology, enzyme activities (intestinal alkaline phosphatase, IAP; dipeptidyl-peptidase IV; sucrase), inducible heat shock proteins, soluble protein and IAP in digesta. Four plasma markers of inflammation (C-reactive protein, haptoglobin, TNF-α and α-acid glycoprotein) were analysed. Treatment effects were analysed by T-test. At day 16, body weights and diversity of intestinal microbiota did not differ between the groups. However, an aberrant composition was observed in the jejunum and ileum of SM pigs [lower abundance of several presumed beneficial microbial groups (lactobacilli, butyrogenic species) and increase in a number of potential pathogens]. Jejunal crypts were deeper (P<0.05), ileal surface area tended to be larger (P=0.080) and colon crypts tended to be narrower (P=0.056) in CM pigs. Sucrase activity in the jejunal mucosa was lower in CM pigs (P<0.05) (other enzymes in jejunal and ileal tissue unaffected). Soluble protein and IAP activity were lower in ileal (P<0.05, both) and colonic (P<0.05 and P<0.01, respectively) digesta of CM pigs. Finally HSP70 relative concentration tended (P=0.096) to be lower in jejunal tissue. HSP27 tended to be lower in the ileum (P=0.064) but was higher in the colon (P<0.05) of CM pigs. Systemic inflammation did not differ between treatments. Neonatal microbiota complexity profoundly affected various aspects of gut tissue and digesta characteristics, according to distinct regional patterns in pigs. CM reduced jejunal maturity, tended to reduce bacterial-induced stress on the intestine but increased it on the colon. Finally, gut luminal degradation potential was higher in CM pigs.

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R.A. Dekker

Wageningen University and Research Centre

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A.J.M. Jansman

Wageningen University and Research Centre

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Hauke Smidt

Wageningen University and Research Centre

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Mieke van den Heuvel

Erasmus University Rotterdam

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A.H. Jan Danser

Erasmus University Rotterdam

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Dirk J. Duncker

Erasmus University Rotterdam

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Jing Zhang

Wageningen University and Research Centre

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Oana Sorop

Erasmus University Rotterdam

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