Based on a presentation at the Meat Science and Muscle Biology Symposium titled "In utero factors... more Based on a presentation at the Meat Science and Muscle Biology Symposium titled "In utero factors that infl uence postnatal muscle growth, carcass composition, and meat quality" at the
Background: Angiopoietin-like 4 (ANGPTL4) has been suggested to play a role in lipid metabolism a... more Background: Angiopoietin-like 4 (ANGPTL4) has been suggested to play a role in lipid metabolism as a regulatory protein of lipoprotein lipase activity. Intestinal secretion of ANGPTL4, which is regulated by fatty acids, may inhibit the activity of circulating lipoprotein lipase; but, recent studies suggest that it could also inhibit pancreatic lipase in the gut and thereby reduce intestinal uptake of lipids. Secretion of the ANGPTL4 protein to either the lumen or tissue/blood side of the intestinal epithelial layer would indicate possible modes of action.Methods: Caco-2 cells were grown on permeable membranes and cultured for 21 days to spontaneously differentiate into an intact monolayer of intestinal cells, mimicking the epithelial cell layer lining the intestinal wall. Cells were treated with 9 mM butyrate and the time dependent gene expression and protein secretion to the apical and basolateral side was analysed over a time-course of 24 hours. Possible feedback from ANGPTL4 prot...
This intervention study was designed as cross-over (four women, one man) with three doses of blac... more This intervention study was designed as cross-over (four women, one man) with three doses of black currant/apple (1:1) juice (750, 1000, and 1500 mL) for one week corresponding to an intake of 4.8, 6.4, and 9.6 mg quercetin per day. Urinary excretion of quercetin increased significantly with dose and with time. The fraction excreted in urine was constant 0.29-0.47%. Plasma quercetin did not change with juice intervention. Plasma ascorbate increased during intervention due to ascorbate from the juice. Total plasma malondialdehyde decreased with time during 1500 mL juice intervention. Plasma protein 2-adipic semialdehyde residues, increased with time and dose, and glutathione peroxidase increased with juice dose, whereas other selected markers of oxidative status did not change. These effects might be related to several components of the juice and cannot be attributed solely to its quercetin content.
The occurrence of wooden breast (WB) in broiler production is increasing, but onset of its develo... more The occurrence of wooden breast (WB) in broiler production is increasing, but onset of its development is only described in part. In this study, we determined the regulation of marker genes related to oxidative stress in Ross308 broilers categorized as no-, mild-or severe-WB, on days 21 and 30 of production. The biochemical parameters, lactate dehydrogenase and pro-and macro-glycogen, were also determined. On day 21, breast meat from birds affected severely by WB had increased mRNA abundances of heat-shock protein 70, heme-oxygenase 1, cyclooxygenase 2, tumor necrosis factor 1, and hypoxia inducible factors as well as higher pH and lower dry matter contents. On day 30, breast meat from both mild and severely affected birds had increased mRNA for heme oxygenase 1, lactate dehydrogenase, and hypoxia inducible factor. Moreover, pro-and micro-glycogen, as well as the total pool of glycogen, were decreased compared with the non-WB birds. In conclusion, this study indicates oxidative stress, inflammation and hypoxic conditions in WB.
Epidemiological studies indicate that moderate alcohol consumption, particularly wine, reduce the... more Epidemiological studies indicate that moderate alcohol consumption, particularly wine, reduce the risk of CHD. The present study was designed to investigate the effect of grape-skin extract on markers of oxidative status. The study was designed as a randomised crossover. A diet with a low content of flavonoids was served with strict control of intake in two consecutive 1-week intervention periods to fifteen subjects (nine women, six men) divided randomly into two groups. During one of the weeks the subjects from either group consumed 200 ml grape-skin extract in water (1 mg extract/ml) at each of three daily meals (31·3 mg total phenolics, including 9·0 mg catechin). An increased activity of glutathione reductase and a borderline increase of glutathione peroxidase activity in erythrocytes were observed after grape-skin intervention, while the intervention had no significant effect on superoxide dismutase or catalase. Likewise, no effect was found on 2-aminoadipic semialdehyde (AAS) ...
The physiological effects of the Stevia-derived compounds, rebaudioside A, stevioside and steviol... more The physiological effects of the Stevia-derived compounds, rebaudioside A, stevioside and steviol have been the focus of several studies due to their use as sweeteners in food. Despite that, little is known about their potential food-drug interactions. In the present study, IPEC-J2 cells and primary hepatocytes were used to investigate the effect of rebaudioside A, stevioside and steviol on cytochrome p450 (CYP) mRNA expression. Moreover, hepatic microsomes were used to investigate direct interactions between the compounds and specific CYP activity. In IPEC-J2 no changes in mRNA expression of CYP1A1 or CYP3A29 were observed with the Stevia-derived compounds. In primary hepatocytes all three tested compounds induced a significant increase in CYP3A29 expression. The tested compounds had no direct effect on specific CYP activity. In conclusion, rebaudioside A, stevioside and steviol induce only minor or no changes to the CYP expression and activity, and are not likely to cause food-dru...
Heart failure is a significant cause of mortality worldwide, and most current therapies treat onl... more Heart failure is a significant cause of mortality worldwide, and most current therapies treat only its symptoms. The results of cardiac stem cell research suggest a promising treatment option for heart failure, but there is currently an unmet demand for better research models. We have therefore, for the first time, isolated, expanded and differentiated progenitor cells obtained from juvenile pig hearts to use as a platform for cardiac stem cell research. Progenitor cells were isolated from the left ventricles of porcine hearts using collagenase enzymatic digestion and Percoll®-gradient centrifugation. Cells were proliferated in Matrigel®-coated wells. Cell differentiation was initiated by applying 5-azacytidine and subsequently controlled by modifying the serum concentration. Western blotting and qPCR were used to determine protein and gene expression, respectively. Cardiac-specific genes, from the following proteins: troponin I-3, and myosin-heavy-chain 7 were stably expressed duri...
Seven men and seven women participated in a randomized crossover trial to study the effect of int... more Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley (Petroselinum crispum), containing high levels of the flavone apigenin, on the urinary excretion of flavones and on biomarkers for oxidative stress. The subjects received a strictly controlled diet low in flavones and other naturally occurring antioxidants during the 2 weeks of intervention. This basic diet was supplemented with parsley providing 3·73–4·49 mg apigenin/MJ in one of the intervention weeks. Urinary excretion of apigenin was 1·59–409·09 μg/MJ per 24 h during intervention with parsley and 0–112·27 μg/MJ per 24 h on the basic diet (P < 0·05). The fraction of apigenin intake excreted in the urine was 0·58 (se 0·16) % during parsley intervention. Erythrocyte glutathione reductase (EC 1.6.4.1; GR) and superoxide dismutase (EC 1.15.1.1; SOD) activities increased during intervention with parsley (P < 0·005) as compared with the levels on the basic diet, whereas...
In this review we describe a new target for food functionality, the taste receptors in the gastro... more In this review we describe a new target for food functionality, the taste receptors in the gastrointestinal tract. These receptors are involved in an intricate signalling network for monitoring of taste and nutrient intake, homeostasis and energy metabolism, and they are also an early warning system for toxic substances in our diet. Especially the receptors for bitter taste provide a new possibility to activate a number of health related signalling pathways, already at low concentrations of the active substance, without requiring uptake into the body and transport via the circulation. When ligands bind to these receptors, signalling is induced either via peptide hormones into the circulation to other organs in the body, or via nerve fibers directly to the brain.
Pigs have often been suggested to be a useful model for humans, when investigating CYP dependent ... more Pigs have often been suggested to be a useful model for humans, when investigating CYP dependent events, like drug metabolism. However, comprehensive knowledge about the constitutive expression of the major CYP and corresponding transcription factors is limited. We compared the constitutive mRNA expression of aryl hydrocarbon receptor, constitutive androstane receptor and pregnane X receptor and CYP1A1, CYP1A2, CYP2A, CYP2E1 and CYP3A in liver, adipose tissue, muscle and small intestine in pigs, as well as the expression along the length of the small intestine and colon. Tissue samples were taken from female pigs, and analyzed for gene expression, as well as CYP dependent activity using qPCR and specific probe substrates, respectively. For all investigated transcription factors and CYPs the mRNA expression and activity was highest in the liver. CYP1A1 and CYP3A mRNA expression and activity was shown in all investigated tissues. Along the small intestine and colon the mRNA expression and activity of CYP1A1 and CYP3A was gradually decreased. The results demonstrated, similarity to that reported for humans, and hence adds to the use of pigs as a model for humans.
Insulin resistance in muscles is a major problem associated with Type 2 diabetes. Bioactive compo... more Insulin resistance in muscles is a major problem associated with Type 2 diabetes. Bioactive compounds of plant origin have long been known for possessing anti-diabetic properties. We have studied the effect of the bioactive compounds naringenin (dihydroflavonol) and falcarinol (polyacetylene) on glucose uptake (GU) in normal and insulin resistant primary porcine myotubes, in the presence and absence of insulin to identify signaling pathways mediating their effects on GU. The dependence on glucose transporter type 4 (Glut4) activity, insulin signaling and AMP-activated protein kinase (AMPK)-signaling was studied by using the Glut4 inhibitor indinavir, the phosphatidyl inositol-3 kinase (PI3K) and p38 mitogen activated protein kinase (MAPK) inhibitor wortmannin, and the AMPK inhibitor dorsomorphin (DM), respectively. Naringenin and falcarinol stimulated GU was attenuated in the presence of indinavir and wortmannin, indicating a dependence on Glut4 activity as well as PI3K and/or p38MAPK activity. By contrast, DM diminished GU induced by naringenin only, indicating that falcarinol-stimulated GU was independent of AMPK activity. Finally, we show that naringenin and falcarinol enhance phosphorylation of TBC1D1 suggesting that these compounds enhance translocation of Glut4 containing vesicles and thereby GU via a TBC1D1-dependent mechanism.
Natural Antioxidants and Anticarcinogens in Nutrition, Health and Disease, 1999
Background: Epidemiologic studies suggest that foods rich in flavonoids might reduce the risk of ... more Background: Epidemiologic studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease. Objective: Our objective was to investigate the effect of intake of flavonoid-containing black currant and apple juice on urinary excretion of quercetin and on markers of oxidative status. Design: This was a crossover study with 3 doses of juice (750, 1000, and 1500 mL) consumed for 1 wk by 4 women and 1 man corresponding to an intake of 4.8, 6.4, and 9.6 mg quercetin/d. Results: Urinary excretion of quercetin increased significantly with dose and with time. The fraction excreted in urine was 0.29-0.47%. Plasma quercetin did not change with juice intervention. Plasma ascorbate increased during intervention because of the ascorbate in the juice. Total plasma malondialdehyde decreased with time during the 1500-mL juice intervention, indicating reduced lipid oxidation in plasma. Plasma 2-amino-adipic semialdehyde residues increased with time and dose, indicating a prooxidant effect of the juice, whereas erythrocyte 2-aminoadipic semialdehyde and ␥-glutamyl semialdehyde concentrations, Trolox-equivalent antioxidant capacity, and ferric reducing ability of plasma did not change. Glutathione peroxidase activity increased significantly with juice dose. Conclusions: Urinary excretion of quercetin seemed to be a small but constant function of quercetin intake. Short-term, high intake of black currant and apple juices had a prooxidant effect on plasma proteins and increased glutathione peroxidase activity, whereas lipid oxidation in plasma seemed to decrease. These effects might be related to several components of the juice and cannot be attributed solely to its quercetin content.
Dose-response : a publication of International Hormesis Society, 2008
The effects of the bioactive polyacetylenes, falcarinol and falcarindiol, present in carrots, cel... more The effects of the bioactive polyacetylenes, falcarinol and falcarindiol, present in carrots, celery, celeriac and other umbelliferous vegetables, on the stress responses in primary myotube cultures, were studied. Biphasic responses on cellular stress responses in myotube cultures were investigated by exposing them to various concentrations of falcarinol and falcarindiol for 24 h before testing effects of 100 microM H(2)O(2) on the intracellular formation of reactive oxygen species (ROS), transcription of the antioxidative enzyme cytosolic glutathione peroxidase (cGPx), and the heat shock proteins (HSP) HSP70 and HO1. At low concentrations (1.6 to 25 microM) polyacetylenes caused a slightly accelerated intra-cellular ROS formation, increased cGPx transcription and decreased HSP70 and HO1 transcription. The increased cGPx transcription may be interpreted as an adaptive response to the increased ROS formation and may have caused a reduced demand for the protective functions of the HSP...
Epidemiological studies suggest that foods rich in flavonoids might reduce the risk of cardiovasc... more Epidemiological studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease and cancer. The objective of the present study was to investigate the effect of green tea extract (GTE) used as a food antioxidant on markers of oxidative status after dietary depletion of flavonoids and catechins. The study was designed as a 2×3 weeks blinded human cross-over intervention study (eight smokers, eight non-smokers) with GTE corresponding to a daily intake of 18·6 mg catechins/d. The GTE was incorporated into meat patties and consumed with a strictly controlled diet otherwise low in flavonoids. GTE intervention increased plasma antioxidant capacity from 1·35 to 1·56 (P<0·02) in postprandially collected plasma, most prominently in smokers. The intervention did not significantly affect markers in fasting blood samples, including plasma or haemoglobin protein oxidation, plasma oxidation lagtime, or activities of the erythrocyte superoxide dismutase, glutathione...
The aim of this study was to validate previously reported associations between microarray gene ex... more The aim of this study was to validate previously reported associations between microarray gene expression levels and pork quality traits using real-time PCR. Meat samples and meat quality data from 100 pigs were collected from a different pig breed to the one tested by microarray (Large White versus Pietrain) and a different country of origin (Denmark versus Germany). Ten genes (CARP, MB, CSRP3, TNNC1, VAPB, TNNI1, HSPB1, TNNT1, TIMP-1, RAD-like) were chosen from the original microarray study on the basis of the association between gene expression levels and the meat quality traits meat %, back fat, pH24, drip loss %, colour a*, colour b*, colour L*, WB-SF, SFA, MUFA, PUFA. Real-time PCR detection methods were developed for validation of all ten genes, confirming association with drip loss (two of two genes), ultimate pH (three of four genes), a* (redness) (two of six genes) and L*(lightness) (two of four genes). Furthermore, several new correlations for MUFA and PUFA were established due to additional meat quality trait information on fatty acid composition not available for the microarray study. Regression studies showed that the maximum explanation of the phenotypic variance of the meat quality traits was 50% for the ultimate pH trait using these ten genes only. Additional studies showed that the gene expression of several of the genes was correlated with each other. We conclude that the genes initially selected from the microarray study were robust, explaining variances of the genes for the meat quality traits.
Effects of flavonoids on stress response of myotube cultures was studied by monitoring the releas... more Effects of flavonoids on stress response of myotube cultures was studied by monitoring the release of [ 14 C] taurine, leukotriene production, and 2′,7′-dichlorodihydroflourescein (DCFH 2) oxidation. Stress was induced by hypotonic shock, which was accompanied by cell swelling leading to increased leukotriene production and a concomitant increase in reactive oxygen species and osmolyte release. In this model system, addition of the flavonoids catechin and quercetin decreased leukotriene production, DCFH 2 oxidation, and taurine efflux, indicating a reduction of cellular stress. High concentrations of epigallocatechin gallate (EGCG) and tea extract increased leukotriene production and initial DCFH 2 oxidation, indicating an increased cellular stress (possibly toxicity). However, taurine efflux was reduced, and also longer exposure time as well as lower concentrations of EGCG and tea reduced DCFH 2 oxidation. Trolox and R-tocopherol did not significantly affect taurine efflux or leukotriene production, and it was therefore concluded that suppression of these responses was not confined to redox activity in a myotube culture.
A chicken model for studying the effects of antioxidants in the diet on oxidative status was set ... more A chicken model for studying the effects of antioxidants in the diet on oxidative status was set up. Chickens fed a semi-synthetic diet low in antioxidants showed a remarkable decrease in erythrocyte stability toward H 2 O 2 or 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH), but increases in catalase activity in liver, carbonyls in insoluble muscle proteins, and enhanced lipid oxidation in heattreated liver samples compared to that of conventionally fed chickens. Thus, this chicken model proved to be more susceptible to oxidative changes than conventionally fed chickens, reflecting a low antioxidative defense. Supplementing this low antioxidant diet with 10% apple/broccoli mixture counteracted these changes, except for activity of catalase in the liver and AAPH-induced lysis of erythrocytes. Supplementation with 10% sweet corn only reduced the carbonyl content in insoluble proteins. However, neither low antioxidant diet nor vegetable supplements affected selected antioxidative enzymes or oxidative stability of lipids in heat-treated muscle tissue.
The role of phospholipase A2 in the induction of drip loss from pig muscle has been investigated.... more The role of phospholipase A2 in the induction of drip loss from pig muscle has been investigated. In samples from porcine M. longissimus dorsi, total PLA2 activity as well as mRNA and protein levels of the group VIA iPLA2 (iPLA2-VIA) increased during the initial 4 h post-mortem period. Morphological studies of porcine muscle showed that at 4 h post-mortem, gaps had formed between muscle fibers and that the sarcolemma membrane borders appeared blurred. At the same time iPLA2-VIA protein levels were increased inside muscle fibers and at the sarcolemma. iPLA2-VIA mRNA abundance in samples from different breeds of pigs with variations in drip loss revealed no clear correlation between drip loss level and iPLA2-VIA expression. Together, these data indicate that during the post-mortem period, iPLA2-VIA expression and activity is increased at the muscle fiber membranes. PLA2 activity may affect membrane permeability and consequently the progression of drip formation in porcine muscle.
Based on a presentation at the Meat Science and Muscle Biology Symposium titled "In utero factors... more Based on a presentation at the Meat Science and Muscle Biology Symposium titled "In utero factors that infl uence postnatal muscle growth, carcass composition, and meat quality" at the
Background: Angiopoietin-like 4 (ANGPTL4) has been suggested to play a role in lipid metabolism a... more Background: Angiopoietin-like 4 (ANGPTL4) has been suggested to play a role in lipid metabolism as a regulatory protein of lipoprotein lipase activity. Intestinal secretion of ANGPTL4, which is regulated by fatty acids, may inhibit the activity of circulating lipoprotein lipase; but, recent studies suggest that it could also inhibit pancreatic lipase in the gut and thereby reduce intestinal uptake of lipids. Secretion of the ANGPTL4 protein to either the lumen or tissue/blood side of the intestinal epithelial layer would indicate possible modes of action.Methods: Caco-2 cells were grown on permeable membranes and cultured for 21 days to spontaneously differentiate into an intact monolayer of intestinal cells, mimicking the epithelial cell layer lining the intestinal wall. Cells were treated with 9 mM butyrate and the time dependent gene expression and protein secretion to the apical and basolateral side was analysed over a time-course of 24 hours. Possible feedback from ANGPTL4 prot...
This intervention study was designed as cross-over (four women, one man) with three doses of blac... more This intervention study was designed as cross-over (four women, one man) with three doses of black currant/apple (1:1) juice (750, 1000, and 1500 mL) for one week corresponding to an intake of 4.8, 6.4, and 9.6 mg quercetin per day. Urinary excretion of quercetin increased significantly with dose and with time. The fraction excreted in urine was constant 0.29-0.47%. Plasma quercetin did not change with juice intervention. Plasma ascorbate increased during intervention due to ascorbate from the juice. Total plasma malondialdehyde decreased with time during 1500 mL juice intervention. Plasma protein 2-adipic semialdehyde residues, increased with time and dose, and glutathione peroxidase increased with juice dose, whereas other selected markers of oxidative status did not change. These effects might be related to several components of the juice and cannot be attributed solely to its quercetin content.
The occurrence of wooden breast (WB) in broiler production is increasing, but onset of its develo... more The occurrence of wooden breast (WB) in broiler production is increasing, but onset of its development is only described in part. In this study, we determined the regulation of marker genes related to oxidative stress in Ross308 broilers categorized as no-, mild-or severe-WB, on days 21 and 30 of production. The biochemical parameters, lactate dehydrogenase and pro-and macro-glycogen, were also determined. On day 21, breast meat from birds affected severely by WB had increased mRNA abundances of heat-shock protein 70, heme-oxygenase 1, cyclooxygenase 2, tumor necrosis factor 1, and hypoxia inducible factors as well as higher pH and lower dry matter contents. On day 30, breast meat from both mild and severely affected birds had increased mRNA for heme oxygenase 1, lactate dehydrogenase, and hypoxia inducible factor. Moreover, pro-and micro-glycogen, as well as the total pool of glycogen, were decreased compared with the non-WB birds. In conclusion, this study indicates oxidative stress, inflammation and hypoxic conditions in WB.
Epidemiological studies indicate that moderate alcohol consumption, particularly wine, reduce the... more Epidemiological studies indicate that moderate alcohol consumption, particularly wine, reduce the risk of CHD. The present study was designed to investigate the effect of grape-skin extract on markers of oxidative status. The study was designed as a randomised crossover. A diet with a low content of flavonoids was served with strict control of intake in two consecutive 1-week intervention periods to fifteen subjects (nine women, six men) divided randomly into two groups. During one of the weeks the subjects from either group consumed 200 ml grape-skin extract in water (1 mg extract/ml) at each of three daily meals (31·3 mg total phenolics, including 9·0 mg catechin). An increased activity of glutathione reductase and a borderline increase of glutathione peroxidase activity in erythrocytes were observed after grape-skin intervention, while the intervention had no significant effect on superoxide dismutase or catalase. Likewise, no effect was found on 2-aminoadipic semialdehyde (AAS) ...
The physiological effects of the Stevia-derived compounds, rebaudioside A, stevioside and steviol... more The physiological effects of the Stevia-derived compounds, rebaudioside A, stevioside and steviol have been the focus of several studies due to their use as sweeteners in food. Despite that, little is known about their potential food-drug interactions. In the present study, IPEC-J2 cells and primary hepatocytes were used to investigate the effect of rebaudioside A, stevioside and steviol on cytochrome p450 (CYP) mRNA expression. Moreover, hepatic microsomes were used to investigate direct interactions between the compounds and specific CYP activity. In IPEC-J2 no changes in mRNA expression of CYP1A1 or CYP3A29 were observed with the Stevia-derived compounds. In primary hepatocytes all three tested compounds induced a significant increase in CYP3A29 expression. The tested compounds had no direct effect on specific CYP activity. In conclusion, rebaudioside A, stevioside and steviol induce only minor or no changes to the CYP expression and activity, and are not likely to cause food-dru...
Heart failure is a significant cause of mortality worldwide, and most current therapies treat onl... more Heart failure is a significant cause of mortality worldwide, and most current therapies treat only its symptoms. The results of cardiac stem cell research suggest a promising treatment option for heart failure, but there is currently an unmet demand for better research models. We have therefore, for the first time, isolated, expanded and differentiated progenitor cells obtained from juvenile pig hearts to use as a platform for cardiac stem cell research. Progenitor cells were isolated from the left ventricles of porcine hearts using collagenase enzymatic digestion and Percoll®-gradient centrifugation. Cells were proliferated in Matrigel®-coated wells. Cell differentiation was initiated by applying 5-azacytidine and subsequently controlled by modifying the serum concentration. Western blotting and qPCR were used to determine protein and gene expression, respectively. Cardiac-specific genes, from the following proteins: troponin I-3, and myosin-heavy-chain 7 were stably expressed duri...
Seven men and seven women participated in a randomized crossover trial to study the effect of int... more Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley (Petroselinum crispum), containing high levels of the flavone apigenin, on the urinary excretion of flavones and on biomarkers for oxidative stress. The subjects received a strictly controlled diet low in flavones and other naturally occurring antioxidants during the 2 weeks of intervention. This basic diet was supplemented with parsley providing 3·73–4·49 mg apigenin/MJ in one of the intervention weeks. Urinary excretion of apigenin was 1·59–409·09 μg/MJ per 24 h during intervention with parsley and 0–112·27 μg/MJ per 24 h on the basic diet (P < 0·05). The fraction of apigenin intake excreted in the urine was 0·58 (se 0·16) % during parsley intervention. Erythrocyte glutathione reductase (EC 1.6.4.1; GR) and superoxide dismutase (EC 1.15.1.1; SOD) activities increased during intervention with parsley (P < 0·005) as compared with the levels on the basic diet, whereas...
In this review we describe a new target for food functionality, the taste receptors in the gastro... more In this review we describe a new target for food functionality, the taste receptors in the gastrointestinal tract. These receptors are involved in an intricate signalling network for monitoring of taste and nutrient intake, homeostasis and energy metabolism, and they are also an early warning system for toxic substances in our diet. Especially the receptors for bitter taste provide a new possibility to activate a number of health related signalling pathways, already at low concentrations of the active substance, without requiring uptake into the body and transport via the circulation. When ligands bind to these receptors, signalling is induced either via peptide hormones into the circulation to other organs in the body, or via nerve fibers directly to the brain.
Pigs have often been suggested to be a useful model for humans, when investigating CYP dependent ... more Pigs have often been suggested to be a useful model for humans, when investigating CYP dependent events, like drug metabolism. However, comprehensive knowledge about the constitutive expression of the major CYP and corresponding transcription factors is limited. We compared the constitutive mRNA expression of aryl hydrocarbon receptor, constitutive androstane receptor and pregnane X receptor and CYP1A1, CYP1A2, CYP2A, CYP2E1 and CYP3A in liver, adipose tissue, muscle and small intestine in pigs, as well as the expression along the length of the small intestine and colon. Tissue samples were taken from female pigs, and analyzed for gene expression, as well as CYP dependent activity using qPCR and specific probe substrates, respectively. For all investigated transcription factors and CYPs the mRNA expression and activity was highest in the liver. CYP1A1 and CYP3A mRNA expression and activity was shown in all investigated tissues. Along the small intestine and colon the mRNA expression and activity of CYP1A1 and CYP3A was gradually decreased. The results demonstrated, similarity to that reported for humans, and hence adds to the use of pigs as a model for humans.
Insulin resistance in muscles is a major problem associated with Type 2 diabetes. Bioactive compo... more Insulin resistance in muscles is a major problem associated with Type 2 diabetes. Bioactive compounds of plant origin have long been known for possessing anti-diabetic properties. We have studied the effect of the bioactive compounds naringenin (dihydroflavonol) and falcarinol (polyacetylene) on glucose uptake (GU) in normal and insulin resistant primary porcine myotubes, in the presence and absence of insulin to identify signaling pathways mediating their effects on GU. The dependence on glucose transporter type 4 (Glut4) activity, insulin signaling and AMP-activated protein kinase (AMPK)-signaling was studied by using the Glut4 inhibitor indinavir, the phosphatidyl inositol-3 kinase (PI3K) and p38 mitogen activated protein kinase (MAPK) inhibitor wortmannin, and the AMPK inhibitor dorsomorphin (DM), respectively. Naringenin and falcarinol stimulated GU was attenuated in the presence of indinavir and wortmannin, indicating a dependence on Glut4 activity as well as PI3K and/or p38MAPK activity. By contrast, DM diminished GU induced by naringenin only, indicating that falcarinol-stimulated GU was independent of AMPK activity. Finally, we show that naringenin and falcarinol enhance phosphorylation of TBC1D1 suggesting that these compounds enhance translocation of Glut4 containing vesicles and thereby GU via a TBC1D1-dependent mechanism.
Natural Antioxidants and Anticarcinogens in Nutrition, Health and Disease, 1999
Background: Epidemiologic studies suggest that foods rich in flavonoids might reduce the risk of ... more Background: Epidemiologic studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease. Objective: Our objective was to investigate the effect of intake of flavonoid-containing black currant and apple juice on urinary excretion of quercetin and on markers of oxidative status. Design: This was a crossover study with 3 doses of juice (750, 1000, and 1500 mL) consumed for 1 wk by 4 women and 1 man corresponding to an intake of 4.8, 6.4, and 9.6 mg quercetin/d. Results: Urinary excretion of quercetin increased significantly with dose and with time. The fraction excreted in urine was 0.29-0.47%. Plasma quercetin did not change with juice intervention. Plasma ascorbate increased during intervention because of the ascorbate in the juice. Total plasma malondialdehyde decreased with time during the 1500-mL juice intervention, indicating reduced lipid oxidation in plasma. Plasma 2-amino-adipic semialdehyde residues increased with time and dose, indicating a prooxidant effect of the juice, whereas erythrocyte 2-aminoadipic semialdehyde and ␥-glutamyl semialdehyde concentrations, Trolox-equivalent antioxidant capacity, and ferric reducing ability of plasma did not change. Glutathione peroxidase activity increased significantly with juice dose. Conclusions: Urinary excretion of quercetin seemed to be a small but constant function of quercetin intake. Short-term, high intake of black currant and apple juices had a prooxidant effect on plasma proteins and increased glutathione peroxidase activity, whereas lipid oxidation in plasma seemed to decrease. These effects might be related to several components of the juice and cannot be attributed solely to its quercetin content.
Dose-response : a publication of International Hormesis Society, 2008
The effects of the bioactive polyacetylenes, falcarinol and falcarindiol, present in carrots, cel... more The effects of the bioactive polyacetylenes, falcarinol and falcarindiol, present in carrots, celery, celeriac and other umbelliferous vegetables, on the stress responses in primary myotube cultures, were studied. Biphasic responses on cellular stress responses in myotube cultures were investigated by exposing them to various concentrations of falcarinol and falcarindiol for 24 h before testing effects of 100 microM H(2)O(2) on the intracellular formation of reactive oxygen species (ROS), transcription of the antioxidative enzyme cytosolic glutathione peroxidase (cGPx), and the heat shock proteins (HSP) HSP70 and HO1. At low concentrations (1.6 to 25 microM) polyacetylenes caused a slightly accelerated intra-cellular ROS formation, increased cGPx transcription and decreased HSP70 and HO1 transcription. The increased cGPx transcription may be interpreted as an adaptive response to the increased ROS formation and may have caused a reduced demand for the protective functions of the HSP...
Epidemiological studies suggest that foods rich in flavonoids might reduce the risk of cardiovasc... more Epidemiological studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease and cancer. The objective of the present study was to investigate the effect of green tea extract (GTE) used as a food antioxidant on markers of oxidative status after dietary depletion of flavonoids and catechins. The study was designed as a 2×3 weeks blinded human cross-over intervention study (eight smokers, eight non-smokers) with GTE corresponding to a daily intake of 18·6 mg catechins/d. The GTE was incorporated into meat patties and consumed with a strictly controlled diet otherwise low in flavonoids. GTE intervention increased plasma antioxidant capacity from 1·35 to 1·56 (P<0·02) in postprandially collected plasma, most prominently in smokers. The intervention did not significantly affect markers in fasting blood samples, including plasma or haemoglobin protein oxidation, plasma oxidation lagtime, or activities of the erythrocyte superoxide dismutase, glutathione...
The aim of this study was to validate previously reported associations between microarray gene ex... more The aim of this study was to validate previously reported associations between microarray gene expression levels and pork quality traits using real-time PCR. Meat samples and meat quality data from 100 pigs were collected from a different pig breed to the one tested by microarray (Large White versus Pietrain) and a different country of origin (Denmark versus Germany). Ten genes (CARP, MB, CSRP3, TNNC1, VAPB, TNNI1, HSPB1, TNNT1, TIMP-1, RAD-like) were chosen from the original microarray study on the basis of the association between gene expression levels and the meat quality traits meat %, back fat, pH24, drip loss %, colour a*, colour b*, colour L*, WB-SF, SFA, MUFA, PUFA. Real-time PCR detection methods were developed for validation of all ten genes, confirming association with drip loss (two of two genes), ultimate pH (three of four genes), a* (redness) (two of six genes) and L*(lightness) (two of four genes). Furthermore, several new correlations for MUFA and PUFA were established due to additional meat quality trait information on fatty acid composition not available for the microarray study. Regression studies showed that the maximum explanation of the phenotypic variance of the meat quality traits was 50% for the ultimate pH trait using these ten genes only. Additional studies showed that the gene expression of several of the genes was correlated with each other. We conclude that the genes initially selected from the microarray study were robust, explaining variances of the genes for the meat quality traits.
Effects of flavonoids on stress response of myotube cultures was studied by monitoring the releas... more Effects of flavonoids on stress response of myotube cultures was studied by monitoring the release of [ 14 C] taurine, leukotriene production, and 2′,7′-dichlorodihydroflourescein (DCFH 2) oxidation. Stress was induced by hypotonic shock, which was accompanied by cell swelling leading to increased leukotriene production and a concomitant increase in reactive oxygen species and osmolyte release. In this model system, addition of the flavonoids catechin and quercetin decreased leukotriene production, DCFH 2 oxidation, and taurine efflux, indicating a reduction of cellular stress. High concentrations of epigallocatechin gallate (EGCG) and tea extract increased leukotriene production and initial DCFH 2 oxidation, indicating an increased cellular stress (possibly toxicity). However, taurine efflux was reduced, and also longer exposure time as well as lower concentrations of EGCG and tea reduced DCFH 2 oxidation. Trolox and R-tocopherol did not significantly affect taurine efflux or leukotriene production, and it was therefore concluded that suppression of these responses was not confined to redox activity in a myotube culture.
A chicken model for studying the effects of antioxidants in the diet on oxidative status was set ... more A chicken model for studying the effects of antioxidants in the diet on oxidative status was set up. Chickens fed a semi-synthetic diet low in antioxidants showed a remarkable decrease in erythrocyte stability toward H 2 O 2 or 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH), but increases in catalase activity in liver, carbonyls in insoluble muscle proteins, and enhanced lipid oxidation in heattreated liver samples compared to that of conventionally fed chickens. Thus, this chicken model proved to be more susceptible to oxidative changes than conventionally fed chickens, reflecting a low antioxidative defense. Supplementing this low antioxidant diet with 10% apple/broccoli mixture counteracted these changes, except for activity of catalase in the liver and AAPH-induced lysis of erythrocytes. Supplementation with 10% sweet corn only reduced the carbonyl content in insoluble proteins. However, neither low antioxidant diet nor vegetable supplements affected selected antioxidative enzymes or oxidative stability of lipids in heat-treated muscle tissue.
The role of phospholipase A2 in the induction of drip loss from pig muscle has been investigated.... more The role of phospholipase A2 in the induction of drip loss from pig muscle has been investigated. In samples from porcine M. longissimus dorsi, total PLA2 activity as well as mRNA and protein levels of the group VIA iPLA2 (iPLA2-VIA) increased during the initial 4 h post-mortem period. Morphological studies of porcine muscle showed that at 4 h post-mortem, gaps had formed between muscle fibers and that the sarcolemma membrane borders appeared blurred. At the same time iPLA2-VIA protein levels were increased inside muscle fibers and at the sarcolemma. iPLA2-VIA mRNA abundance in samples from different breeds of pigs with variations in drip loss revealed no clear correlation between drip loss level and iPLA2-VIA expression. Together, these data indicate that during the post-mortem period, iPLA2-VIA expression and activity is increased at the muscle fiber membranes. PLA2 activity may affect membrane permeability and consequently the progression of drip formation in porcine muscle.
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Papers by Jette Young