RESUMO
PURPOSE: The consumption of highly processed food is often associated with a high intake of inorganic phosphate. Hyperphosphatemia is accompanied by an inflammatory status in patients with chronic kidney disease. However, the immune response to high phosphorus intake in healthy individuals is largely unknown. Therefore, the aim of the present study was to evaluate the effect of a single phosphate-enriched meal on inflammasome activity and plasma levels of inflammatory markers. METHODS: The analysis included 28 participants who received a single dose of either 700 mg phosphorus or a placebo with a test meal. At baseline, 4 and 8 h post-meal, plasma interleukin (IL)-6, IL-1ß, IL-10, c-reactive protein (CRP), soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (sgp130) levels were determined. At baseline and 4 h post-meal, peripheral blood mononuclear cells were isolated to assess inflammasome activity. Subsequently, the effect of phosphate with or without glucose on IL-6 and IL-1ß gene expression and secretion in U937 monocytes was examined. RESULTS: While both groups showed a marked postprandial increase in IL-6 plasma levels, neither plasma levels of IL-6, IL-1ß, CRP, IL-10, sIL-6R, and sgp130 nor inflammasome activity were affected by phosphate compared to placebo. In U937 cells, there was also no effect of phosphate on IL-6 expression, but the addition of glucose increased it. Phosphate, however, reduced the IL-1ß secretion of these cells. CONCLUSION: Postprandial inflammatory markers were not affected by dietary phosphate. However, IL-6 plasma levels were markedly increased post-meal, which appears to be a metabolic rather than a pro-inflammatory phenomenon. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03771924, date of registration: 11th December 2018, retrospectively registered.
Assuntos
Interleucina-10 , Interleucina-6 , Humanos , Inflamassomos , Receptor gp130 de Citocina , Leucócitos Mononucleares/metabolismo , Voluntários Saudáveis , Proteína C-Reativa/metabolismo , Glucose , Fosfatos , Período Pós-PrandialRESUMO
Microalgae have drawn increasing attention as sustainable food sources, also because of their lipid-lowering phytosterols. As phytosterols are also discussed critically regarding their effect on the availability of fat-soluble vitamins, this study aimed to investigate microalgae-derived phytosterols and their effect on vitamin D status. GC-MS analysis showed large variations in the phytosterol profiles of microalgal species. The most frequent sterols were ß-sitosterol and stigmasterol. To investigate their effects on vitamin D status, 40 mice were randomized to four groups and fed a vitamin D3-adequate (25 µg/kg) Western-style diet with 0% phytosterols (control) or 1% ergosterol (a fungal sterol not typical for microalgae), ß-sitosterol or stigmasterol for four weeks. Contrary to the hypothesis that phytosterols adversely affect vitamin D uptake, mice fed ß-sitosterol had significantly higher concentrations of vitamin D3 in plasma (3.15-fold, p<0.01), liver (3.15-fold, p<0.05), and skin (4.12-fold, p<0.005) than the control group. Small increases in vitamin D3 in plasma and skin were also observed in mice fed stigmasterol. In contrast, vitamin D3 levels in the ergosterol and control groups did not differ. The increased tissue levels of vitamin D3 in mice fed ß-sitosterol and stigmasterol were not attributable to the observed reduction in liver triglycerides in these groups. The data rather suggest that changes in bile acid profiles were responsible for the beneficial effect of microalgae sterols on the bioavailability of vitamin D3. In conclusion, consumption of microalgae might not adversely affect vitamin D status.
Assuntos
Microalgas , Fitosteróis , Animais , Camundongos , Disponibilidade Biológica , Colecalciferol , Ergosterol , Microalgas/metabolismo , Fitosteróis/metabolismo , Esteróis , Estigmasterol , VitaminasRESUMO
Propionate has antimicrobial activity and is suggested to influence lipid metabolism. Here, we investigated the effect of propionate on lipid metabolism and the gut microbiome in fructose-fed mice as a model of diet-induced steatosis and gut dysbiosis. Therefore, 48 male wild-type mice were fed isoenergetic diets with either 0% fructose (F-) or 40% fructose (F+) that contained 0% propionate (P-) or 1% propionate (P+) for 7 weeks. Mice that received the F+ diets developed fatty livers, had fewer small intestinal proteobacteria and colonic actinobacteria and were characterised by changes in bacterial genera (e.g., Allobaculum, Lachnospiraceae, and Escherichia). Interestingly, mice fed the F+ diets had higher levels of propionate and butyrate in the circulation than mice fed the F- diets (p < 0.05). Treatment with propionate influenced neither hepatic or plasma lipids nor levels of circulating SCFAs. With the exception of Verrucomicrobia, other bacterial phyla were not affected by propionate.
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Ácidos Graxos Voláteis/sangue , Frutose/efeitos adversos , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Propionatos/administração & dosagem , Animais , Bactérias/classificação , Disbiose , Fígado Gorduroso , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Because antibiotic use in livestock is assumed to contribute to the emerging public health crisis of antibiotic resistance, alternatives are required. Phytogenic additives are extensively studied due to their antibiotic properties. Components of Agrimonia species have been reported as candidate antimicrobials that possess antioxidative and anti-inflammatory properties. We studied the impact of Agrimonia procera (AP) on the growth of selected strains of gut bacteria, the effect of AP on the mRNA abundance of genes involved in inflammation and bacterial defense in a colon carcinoma cell line, the effect of AP in piglets challenged with lipopolysaccharides, and the effect of AP on the growth performance of healthy piglets. RESULTS: The in vitro growth rate of different bacteria strains was negatively affected by AP, especially in Pediococcus pentosaceus and all tested E. coli strains. Stimulation of Caco-2 cells with TNFα resulted in elevated mRNA expression of CXCL1, IL-8 and GPX2. After pretreatment of cells with AP, stimulation of Caco-2 cells with TNFα still resulted in elevated mRNA expression of CXCL1 and IL-8 at all measured points in time. However, mRNA expression in AP-pretreated cells was lower after 6 h and 24 h. In addition, expression of DEFB1 and GPX2 was significantly elevated after TNFα stimulation. In vivo, application of lipopolysaccharides induced significantly increased animal body temperatures. Piglets pretreated with AP prior to lipopolysaccharide application showed a faster and larger increase in body temperature than controls. In addition, piglets pretreated with AP appeared to release more TNFα than controls. In healthy piglets, AP treatment had no impact on growth performance parameters. Fecal dry matter and total plasma antioxidant capacity tended to be higher in piglets treated with AP than in control piglets (P = 0.055 and P = 0.087, respectively). CONCLUSIONS: AP has antimicrobial effects in vitro and stimulated the expression of proinflammatory cytokines in Caco-2 cells. The additive had no effect on growth in healthy piglets but increased the immune response in LPS-treated animals. In addition, AP appeared to have antioxidative effects in vivo. Therefore, AP merits testing as a future alternative to antibiotics in animal husbandry.
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Agrimonia , Anti-Infecciosos/farmacologia , Colo/efeitos dos fármacos , Citocinas/metabolismo , Defensinas/metabolismo , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Extratos Vegetais/farmacologia , Agrimonia/química , Animais , Animais Recém-Nascidos , Proteína C-Reativa/análise , Células CACO-2 , Colo/citologia , Escherichia coli/efeitos dos fármacos , Feminino , Humanos , Inflamação/induzido quimicamente , Lacticaseibacillus casei/efeitos dos fármacos , Masculino , Pediococcus pentosaceus/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Suínos , Fator de Necrose Tumoral alfa/sangueRESUMO
Cocoa polyphenols are thought to reduce the risk of cardiovascular diseases. Thus, cocoa-containing foods may have significant health benefits. Here, we studied the impact of chocolate liquor on vascular lesion development and plaque composition in a mouse model of atherosclerosis. Apolipoprotein E (apoE)-knockout mice were assigned to two groups and fed a Western diet that contained 250 g/kg of either chocolate liquor or a polyphenol-free isoenergetic control paste for 16 weeks. In addition to fat, protein, and fibers, the chocolate liquor contained 2 g/kg of polyphenols. Compared with the control group, mice fed the chocolate liquor had larger plaque areas in the descending aorta and aortic root, which were attributed to a higher mass of vascular smooth muscle cells (VSMCs) and collagen. Vascular lipid deposits and calcification areas did not differ between the two groups. The aortic tissue level of interleukin-6 (IL-6) mRNA was 5-fold higher in the mice fed chocolate liquor than in the control mice. Chocolate-fed mice exhibited an increased hepatic saturated to polyunsaturated fatty acid ratio than the controls. Although the chocolate liquor contained 14 µg/kg of vitamin D2, the chocolate liquor-fed mice did not have measurable 25-hydroxyvitamin D2 in the serum. These mice even showed a 25% reduction in the level of 25-hydroxyvitamin D3 compared with the control mice. Overall, present data may contribute to our understanding how chocolate constituents can impact vascular lesion development.
Assuntos
Aterosclerose/terapia , Chocolate , Dieta Hiperlipídica , Placa Aterosclerótica/patologia , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Aterosclerose/genética , Ergocalciferóis/administração & dosagem , Ergocalciferóis/farmacologia , Masculino , Camundongos KnockoutRESUMO
PURPOSE: The Nutrition Societies in Germany, Austria, and Switzerland recommend a daily intake of 20 µg vitamin D3 for adults when endogenous synthesis is absent. The current study aimed to elucidate whether this vitamin D3 dose impacts cardiovascular risk markers of adults during the winter months. METHODS: The study was conducted in Halle (Saale), Germany (51o northern latitude) as a placebo-controlled, double-blinded, randomised trial (from January to April). A total of 105 apparently healthy subjects (male and female, 20-71 years old) were included. Subjects were randomly allocated to two groups. One group received a daily 20-µg vitamin D3 dose (n = 54), and the other group received a placebo (n = 51) for 12 weeks. Outcome measures included blood pressure, heart rate, concentrations of renin, aldosterone, serum lipids and vascular calcification markers, and haematologic variables such as pro-inflammatory monocytes. RESULTS: Blood pressure and systemic cardiovascular risk markers remained unchanged by vitamin D3 supplementation, although serum 25-hydroxyvitamin D3 increased from 38 ± 14 to 73 ± 16 nmol/L at week 12. The placebo and vitamin D groups did not differ in their final cardiovascular risk profile. CONCLUSION: Daily supplementation of 20 µg vitamin D3 during winter is unlikely to change cardiovascular risk profile.
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Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Colecalciferol/administração & dosagem , Deficiência de Vitamina D/complicações , Adulto , Idoso , Pressão Sanguínea , Calcifediol/sangue , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Placebos , Fatores de Risco , Estações do AnoRESUMO
BACKGROUND: Growing evidence suggests that disintegrin and metalloprotease (ADAM) 17 (ADAM17) and ADAM10 contribute to the pathogenesis of vascular diseases. ADAM17 promotes inflammatory processes by liberating tumor necrosis factor α, interleukin 6 receptor (IL-6R), and tumor necrosis factor receptor 1 (TNFR1). ADAM17 and ADAM10 modulate vascular permeability by cleaving endothelial adhesion molecules such as junctional adhesion molecule A (JAM-A) and vascular endothelial cadherin (VE-cadherin), respectively. OBJECTIVE: This study was designed to investigate whether a link might exist between the protective effects of fish oil (FO) supplementation against atherosclerosis and ADAM function. METHODS: Male LDL receptor knockout (LDLR(-/-)) mice and male wild-type (WT) mice were fed a Western diet (200 g/kg fat, 1.5 g/kg cholesterol) containing either 20% lard (LDLR(-/-)-lard and WT-lard groups) or 10% lard combined with 10% FO (LDLR(-/-)-FO and WT-FO groups) for 12 wk. Atherosclerotic lesion development and fatty acid composition of liver microsomes were evaluated. ADAM10 and ADAM17 expression was determined by quantitative real-time polymerase chain reaction and immunoblot analyses. Concentrations of soluble ADAM substrates in plasma and liver extracts were measured by ELISA. RESULTS: Diets supplemented with FO markedly reduced development of early atherosclerotic lesions in LDLR(-/-) mice (LDLR(-/-)-lard group vs. LDLR(-/-)-FO group mean ± SD: 29.6 ± 6.1% vs. 22.5 ± 4.2%, P < 0.05). This was not accompanied by changes in expression of ADAM17 or ADAM10 in the aorta or liver. No dietary effects on circulating TNFR1 (LDLR(-/-)-lard group vs. LDLR(-/-)-FO group mean ± SD: 1.22 ± 0.23 vs. 1.39 ± 0.28, P > 0.2) or IL-6R (1.06 ± 0.12 vs. 0.98 ± 0.09 fold of WT-lard group, P > 0.1), classical substrates of ADAM17 on macrophages, and neutrophil granulocytes were observed. However, a reduction in atherosclerotic lesions in the LDLR(-/-)-FO group was accompanied by a significant reduction in the circulating endothelial cell adhesion molecules JAM-A (LDLR(-/-)-lard group vs. LDLR(-/-)-FO group mean ± SD: 1.42 ± 0.20 vs. 0.95 ± 0.56 fold of WT-lard group, P < 0.05), intercellular adhesion molecule 1 (1.15 ± 0.14 vs. 0.88 ± 0.17 fold of WT-lard group, P < 0.05), and VE-cadherin (0.88 ± 0.12 vs. 0.72 ± 0.15 fold of WT-lard group, P < 0.05), reflecting reduced ADAM activity in endothelial cells. CONCLUSION: FO exerted an antiatherogenic effect on male LDLR(-/-) mice that was accompanied by a reduced release of ADAM17 and ADAM10 substrates from endothelial cells. It is suggested that FO-decreased ADAM activity contributes to improved endothelial barrier function and thus counteracts intimal lipoprotein insudation and macrophage accumulation.
Assuntos
Proteínas ADAM/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Suplementos Nutricionais , Óleos de Peixe/farmacologia , Proteínas de Membrana/metabolismo , Proteínas ADAM/genética , Proteína ADAM10 , Proteína ADAM17 , Secretases da Proteína Precursora do Amiloide/genética , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/efeitos adversos , Dieta Ocidental/efeitos adversos , Gorduras na Dieta/administração & dosagem , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de LDL/genética , Receptores de LDL/metabolismoRESUMO
Conglutin γ and phytate are considered as potential biofunctional compounds of lupin protein isolate, but their impact on vascular health is unknown. This study aimed to investigate the effect of conglutin γ and phytate, respectively, on circulating levels of sterols, markers of cholesterol biosynthesis and minerals, and on the development and progression of aortic lesions in apoE-deficient mice. To this end, mice were fed a western diet with either casein (200 g/kg; served as a control), conglutin γ from L. angustifolius (200 g/kg) or casein (200 g/kg) supplemented with phytate (5 g/kg) for 16 weeks. Here we found that conglutin γ but not phytate was capable of reducing the circulating concentration of cholesterol. Plasma levels of desmosterol and lathosterol as markers of the cholesterol synthesis were not affected, and 7-dehydrocholesterol was even higher in mice fed conglutin γ than in mice fed casein or casein + phytate. All mice developed pronounced aortic lesions, but histological characterization of plaque area and composition showed no differences between the three groups of mice. Conclusively, conglutin γ exerts cholesterol-lowering effects but appears to have no anti-atherosclerotic properties in the apoE-deficient mice. Phytate neither affected plasma cholesterol nor aortic lesion development.
Assuntos
Colesterol/sangue , Lupinus/química , Ácido Fítico/isolamento & purificação , Proteínas de Plantas/isolamento & purificação , Animais , Apolipoproteínas E/sangue , Biomarcadores/sangue , Desidrocolesteróis/sangue , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Knockout , Ácido Fítico/farmacologia , Proteínas de Plantas/farmacologia , Oligoelementos/sangue , Vitamina D/sangueRESUMO
Vitamin D insufficiency is highly associated with cardiovascular morbidity and mortality. We have demonstrated enhanced vascular calcification in LDL receptor knockout (LDLR(-/-)) mice fed a diet low in vitamin D. This study aimed to investigate the impact of a diet low in vitamin D on vascular calcification in wild-type (WT) mice lacking atherosclerotic plaques and the effects of a persistent and discontinuous vitamin D insufficiency on atherosclerotic plaque composition in LDLR(-/-) mice. The study was performed with 4-wk-old male WT and LDLR(-/-) mice that were fed a normal calcium/phosphate Western diet (210 g/kg fat, 1.5 g/kg cholesterol) containing either adequate (+D; 1000 IU/kg) or low (-D; 50 IU/kg) amounts of vitamin D-3 for 16 wk. Four groups of LDLR(-/-) mice received 1 of the 2 diets for additional 16 wk (total 32 wk) and were compared with mice fed the diets for only 16 wk. WT and LDLR(-/-) mice that were fed the -D diet for 16 wk tended to develop more calcified spots in the aortic valve than mice fed the +D diet (+50% and +56%, respectively; P < 0.10). In LDLR(-/-) mice, the extent of calcification increased from week 16 to week 32 and was higher in the -D than in the +D group (P < 0.05). The calcification, owing to the -D diet, was accompanied by highly expressed osteoblast differentiation factors, indicating a transdifferentiation of vascular cells to osteoblast-like cells. Feeding the +D diet subsequent to the -D diet reduced the vascular calcification (P < 0.05). LDLR(-/-) mice fed the -D diet for 32 wk had higher plaque lipid depositions (+48%, P < 0.05) and a higher expression of cluster of differentiation 68 (+31%, P < 0.05) and tumor necrosis factor α (+134%, P < 0.001) than the +D group. Collectively, the findings imply low vitamin D status as a causal factor for vascular calcification and atherosclerosis.
Assuntos
Ração Animal , Osteoblastos/patologia , Receptores de LDL/genética , Calcificação Vascular/patologia , Deficiência de Vitamina D/patologia , Vitamina D/sangue , 24,25-Di-Hidroxivitamina D 3/sangue , Animais , Aorta/metabolismo , Aorta/patologia , Calcitriol/sangue , Cálcio/sangue , Colecalciferol/sangue , Genótipo , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Fosfatos/sangue , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Receptores de LDL/metabolismo , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/metabolismo , Vitamina D/farmacologia , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/metabolismo , Vitaminas/sangue , Vitaminas/farmacologiaRESUMO
BACKGROUND: The weaning period is critical for stress-related diseases and infections. Currently, large amounts of therapeutic antimicrobials are used to treat infections in the livestock production, especially in piglets. Phytogenic feed additives could provide a useful alternative. We hypothesize, that components in agrimonia species which have been used successfully in humans to treat gastrointestinal infections could also improve the health of piglets. We investigated the effects of Agrimonia procera (AP) on the growth performance of piglets and cytokine expression in isolated porcine peripheral blood mononuclear cells (PBMC). RESULTS: Here we show that piglets that received a diet with 0.56 g/kg AP for 6 weeks tended to ingest more food (+5.1%; P < 0.10), and were characterized by a higher nitrogen retention (+9.6%, P < 0.05) than the control group without AP treatment. Data from a second experiment reveal that piglets fed a diet with 0.87 g/kg AP for 6 weeks had an improved food conversion ratio (1.46 ± 0.04) compared to those that received none (1.54 ± 0.08) or 8.7 g/kg AP (1.60 ± 0.08) with their diets (P < 0.001). However, the food intake, daily weight gain and dry matter of feces were not affected by the AP treatment. Treatment of PBMC for 1 and 6 h with AP extract (APE) reduced the mRNA abundance of tumor necrosis factor (TNF)? in cells challenged with lipopolysaccharides (LPS) but not in cells without LPS stimulation (P < 0.05). The lower mRNA expression of TNF? was accompanied by a trend towards a lower release of TNF? from these cells (P?=?0.067). After the treatment of PBMC with APE for 6 h, the relative mRNA concentration of interleukin (IL)-1? declined (P < 0.05), whereas that of IL-10 remained unchanged. Treatment of LPS-challenged PBMC for 20 h with varying concentrations of APE did not reveal any effect on cytokine expression and TNF? release. CONCLUSIONS: The results indicate that low dosages of AP may improve the growth performance of piglets and seem to exert antiinflammatory effects in porcine immune cells challenged with LPS.
Assuntos
Agrimonia , Ração Animal/análise , Dieta/veterinária , Suínos/crescimento & desenvolvimento , Fenômenos Fisiológicos da Nutrição Animal , Animais , Citocinas/genética , Citocinas/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , DesmameRESUMO
There is limited data on the effect of UV light exposure versus orally ingested vitamin D3 on vitamin D metabolism and health. A 4-week study with 16 pigs (as a model for human physiology) was conducted. The pigs were either supplemented with 20 µg/d vitamin D3 or exposed to UV light for 19 min/d to standardise plasma 25-hydroxyvitamin D3 levels. Important differences were higher levels of stored vitamin D3 in skin and subcutaneous fat, higher plasma concentrations of 3-epi-25-hydroxyvitamin D3 and increases of cutaneous lumisterol3 in UV-exposed pigs compared to supplemented pigs. UV light exposure compared to vitamin D3 supplementation resulted in lower hepatic cholesterol, higher circulating plasma nitrite, a marker of the blood pressure-lowering nitric oxide, and a reduction in the release of pro- and anti-inflammatory cytokines from stimulated peripheral blood mononuclear cells. However, plasma metabolome and stool microbiome analyses did not reveal any differences between the two groups. To conclude, the current data show important health relevant differences between oral vitamin D3 supplementation and UV light exposure. The findings may also partly explain the different vitamin D effects on health parameters obtained from association and intervention studies.
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CONTEXT: Hyperphosphatemia and high levels of fibroblast growth factor 23 (FGF23) are risk factors for cardiovascular events in patients with chronic kidney diseases. However, the impact of an inorganic phosphorus additive in healthy people is largely unknown. OBJECTIVE: We aimed to investigate the acute effect of excessive dietary phosphorus administered as sodium dihydrogen phosphate on the postprandial levels of Pi and FGF23 and the response to food. METHODS: This study was a double-blind placebo-controlled crossover study with 29 healthy male and female participants from the general community who were administered a single dose of either 700 mg phosphorus (NaH2PO4) or a sodium-adjusted placebo in combination with a test meal. Postprandial plasma levels of Pi and FGF23 were measured. RESULTS: Compared with placebo, oral phosphorus increased the plasma Pi level, which remained elevated during the ensuing 8 hours (at 480 minutes: 1.31 vs 1.16 mmol/l; Pâ <â 0.001), increased urinary Pi (iAUC0-480 789 vs 95 mmol/mmol; Pâ <â 0.001), reduced tubular Pi reabsorption (iAUC0-480 -31.5 vs -6.2; Pâ <â 0.001), decreased urinary calcium (iAUC0-240 30.6 vs 53.0 mmol/mmol; Pâ =â 0.009), and stimulated the release of parathyroid hormone (iAUC0-480 2212 vs 768 ng/l; Pâ <â 0.001). However, the FGF23 levels did not change. Postprandial levels of glucose, insulin, and lipids were not substantially affected by phosphorus vs placebo. CONCLUSION: An oral phosphorus load can induce elevated postprandial levels of circulating Pi for hours in healthy subjects, despite rapid homeostatic counterreactions. FGF23 levels and the postprandial response to food were not affected.
Assuntos
Suplementos Nutricionais , Fator de Crescimento de Fibroblastos 23/sangue , Fosfatos/administração & dosagem , Administração Oral , Adolescente , Adulto , Fatores de Risco Cardiometabólico , Estudos Cross-Over , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Fosfatos/efeitos adversos , Fosfatos/sangue , Período Pós-Prandial , Adulto JovemRESUMO
Fermentable carbohydrates are gaining interest in the field of human nutrition because of their benefits in obesity-related comorbidities. The aim of this study was to investigate the influence of fermentable carbohydrates, such as pectin and inulin, in an atherogenic diet on metabolic responses and plaque formation in coronary arteries using a Saddleback pig model. Forty-eight healthy pigs aged five months were divided into four feeding groups (n = 10) and one baseline group (n = 8). Three feeding groups received an atherogenic diet (38% crisps, 10% palm fat, and 2% sugar with or without supplementation of 5% pectin or inulin), and one group received a conventional diet over 15 weeks. Feed intake, weight gain, body condition score, and back fat thickness were monitored regularly. Blood and fecal samples were collected monthly to assess the metabolites associated with high cardiovascular risk and fat content, respectively. At the end of 15 weeks, the coronary arteries of the pigs were analyzed for atherosclerotic plaque formation. Independent of supplementation, significant changes were observed in lipid metabolism, such as an increase in triglycerides, bile acids, and cholesterol in serum, in all groups fed atherogenic diets in comparison to the conventional group. Serum metabolome analysis showed differentiation of the feeding groups by diet (atherogenic versus conventional diet) but not by supplementation with pectin or inulin. Cardiovascular lesions were found in all feeding groups and in the baseline group. Supplementation of pectin or inulin in the atherogenic diet had no significant impact on cardiovascular lesion size. Saddleback pigs can develop naturally occurring plaques in coronary arteries. Therefore, this pig model offers potential for further research on the effects of dietary intervention on obesity-related comorbidities, such as cardiovascular lesions, in humans.
Assuntos
Vasos Coronários , Inulina , Animais , Ácidos e Sais Biliares , Colesterol , Vasos Coronários/metabolismo , Dieta , Dieta Aterogênica , Suplementos Nutricionais , Humanos , Inulina/metabolismo , Inulina/farmacologia , Obesidade/metabolismo , Pectinas , Açúcares , Suínos , TriglicerídeosRESUMO
Homocysteine is associated with several diseases, and a series of dietary factors are known to modulate homocysteine levels. As mice are often used as model organisms to study the effects of dietary hyperhomocysteinemia, we collected data about concentrations of vitamin B12, vitamin B6, folate, methionine, cystine, and choline in mouse diets and the associated plasma/serum homocysteine levels. In addition, we more closely examined the composition of the control diet, the impact of the mouse strain, sex and age, and the duration of the dietary intervention on homocysteine levels. In total, 113 out of 1103 reviewed articles met the inclusion criteria. In the experimental and control diets, homocysteine levels varied from 0.1 to 280 µmol/l. We found negative correlations between dietary vitamin B12 (rho = - 0.125; p < 0.05), vitamin B6 (rho = - 0.191; p < 0.01) and folate (rho = - 0.395; p < 0.001) and circulating levels of homocysteine. In contrast, a positive correlation was observed between dietary methionine and homocysteine (methionine: rho = 0.146; p < 0.05). No significant correlations were found for cystine or choline and homocysteine levels. In addition, there was no correlation between the duration of the experimental diets and homocysteine levels. More importantly, the data showed that homocysteine levels varied widely in mice fed control diets as well. When comparing control diets with similar nutrient concentrations (AIN-based), there were significant differences in homocysteine levels caused by the strain (ANOVA, p < 0.05) and age of the mice at baseline (r = 0.47; p < 0.05). When comparing homocysteine levels and sex, female mice tended to have higher homocysteine levels than male mice (9.3 ± 5.9 µmol/l vs. 5.8 ± 4.5 µmol/l; p = 0.069). To conclude, diets low in vitamin B12, vitamin B6, or folate and rich in methionine are similarly effective in increasing homocysteine levels. AIN recommendations for control diets are adequate with respect to the amounts of homocysteine-modulating dietary parameters. In addition, the mouse strain and the age of mice can affect the homocysteine level.
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Protein from lupin is supposed to have anti-atherogenic effects due to its lipid-lowering properties in laboratory animals. It is further suggested that the amino acid cysteine plays a crucial role in this aspect. The objective of the present study was to compare the effects of lupin protein and cysteine-supplemented casein with those of casein on atherosclerotic lesion development in apoE-deficient mice. For that purpose, thirty mice were fed an egg albumin-based Western-type diet containing test protein (100 g/kg) for 4 months. ApoE-deficient mice fed the lupin protein or the cysteine-supplemented casein had more than 50 % less aortic calcification than mice fed casein (P < 0.05). The quantified lesion area as a percentage of the total surface area, as well as the collagen and fat content of the lesions were not different between the three groups of mice. The concentration of VLDL TAG was higher in mice fed the lupin protein and the cysteine-supplemented casein than in mice fed casein (P < 0.05). The cholesterol concentrations of VLDL, LDL and HDL from mice fed the lupin protein and cysteine-supplemented casein were not different compared with the mice fed casein. Also, the plasma concentrations of homocysteine, Ca, inorganic phosphate, and the activity of glutathione peroxidase in plasma and liver did not differ between the three groups of mice. The present study shows that lupin protein and cysteine-supplemented casein compared with casein reduce the calcification of atherosclerotic lesions in apoE-deficient mice. This effect seems not to be mediated by effects on plasma lipoproteins, homocysteine and circulating minerals.
Assuntos
5'-Nucleotidase/isolamento & purificação , 5'-Nucleotidase/farmacologia , Apolipoproteínas E/deficiência , Aterosclerose/prevenção & controle , Calcinose/prevenção & controle , Caseínas/farmacologia , Cistina/farmacologia , 5'-Nucleotidase/uso terapêutico , Aminoácidos/análise , Ração Animal , Animais , Aterosclerose/patologia , Primers do DNA , Proteínas Alimentares/administração & dosagem , Modelos Animais de Doenças , Ingestão de Energia , Lipídeos/sangue , Lipídeos/fisiologia , Camundongos , Camundongos Knockout/genética , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Lupin protein had hypocholesterolemic effects in laboratory animals. However, the effect in humans has not been elucidated till now. AIM OF THE STUDY: To investigate the effect of lupin protein on circulating cholesterol in plasma and lipoproteins of hypercholesterolemic subjects. SUBJECTS AND METHODS: A randomised, double-blind, placebo-controlled, parallel trial (23 females and 20 males completed the trial) was conducted to compare the effects of lupin protein versus casein as control protein on plasma lipids and amino acids. Thirty-five grams of the test protein were consumed daily for 6 weeks. RESULTS: Both lupin protein and casein resulted in a reduction of circulating plasma cholesterol (-0.50 +/- 0.64 and -0.47 +/- 0.79 mM; P < 0.05) from baseline to week 6. The reduction of plasma cholesterol was mainly caused by a reduction of LDL cholesterol in the lupin protein group (-0.31 +/- 0.46 mM; P < 0.05), while in the casein group HDL cholesterol significantly declined (-0.17 +/- 0.15 mM; P < 0.05). Comparing the lupin protein group with the casein group yielded a difference in the net changes from baseline to week 6 in the LDL:HDL cholesterol-ratio of -0.24 (95% CI: -0.007, -0.479; P < 0.05). No significant differences in net changes were observed for plasma concentrations of triglycerides, glucose, homocysteine, taurine and most of the amino acids. CONCLUSIONS: Lupin protein compared to casein slightly lowered the concentration of LDL cholesterol in hypercholesterolemic subjects, without altering HDL cholesterol. No or minor effects of lupin protein were observed on circulating glucose, homocysteine and plasma amino acids.
Assuntos
Caseínas/administração & dosagem , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Proteínas Alimentares/administração & dosagem , Hipercolesterolemia/dietoterapia , Lupinus , Proteínas de Plantas/administração & dosagem , Adulto , Idoso , Aminoácidos/sangue , Glicemia/análise , Caseínas/efeitos adversos , Proteínas Alimentares/efeitos adversos , Método Duplo-Cego , Feminino , Alimentos Formulados/efeitos adversos , Regulação da Expressão Gênica , Humanos , Lupinus/química , Masculino , Pessoa de Meia-Idade , Fitoterapia/efeitos adversos , Proteínas de Plantas/efeitos adversos , Sementes/química , Triglicerídeos/sangue , Adulto JovemRESUMO
BACKGROUND: Oxidative stress is supposed to increase lipid accumulation by stimulation of hepatic lipogenesis at transcriptional level. This study was performed to investigate the role of glutathione in the regulation of this process. For that purpose, male rats were treated with buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, for 7 days and compared with untreated control rats. RESULTS: BSO treatment caused a significant reduction of total glutathione in liver (-70%), which was attributable to diminished levels of reduced glutathione (GSH, -71%). Glutathione-deficient rats had lower triglyceride concentrations in their livers than the control rats (-23%), whereas the circulating triglycerides and the cholesterol concentrations in plasma and liver were not different between the two groups of rats. Livers of glutathione-deficient rats had lower mRNA abundance of sterol regulatory element-binding protein (SREBP)-1c (-47%), Spot (S)14 (-29%) and diacylglycerol acyltransferase 2 (DGAT-2, -27%) and a lower enzyme activity of fatty acid synthase (FAS, -26%) than livers of the control rats. Glutathione-deficient rats had also a lower hepatic activity of the redox-sensitive protein-tyrosine phosphatase (PTP)1B, and a higher concentration of irreversible oxidized PTP1B than control rats. No differences were observed in protein expression of total PTP1B and the mature mRNA encoding active XBP1s, a key regulator of unfolded protein and ER stress response. CONCLUSION: This study shows that glutathione deficiency lowers hepatic triglyceride concentrations via influencing lipogenesis. The reduced activity of PTP1B and the higher concentration of irreversible oxidized PTP1B could be, at least in part, responsible for this effect.
Assuntos
Regulação para Baixo , Glutationa/deficiência , Lipogênese/genética , Fígado/metabolismo , Estresse Oxidativo , Proteínas Tirosina Fosfatases/metabolismo , Animais , Butionina Sulfoximina/administração & dosagem , Butionina Sulfoximina/farmacologia , Colesterol/sangue , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Lipogênese/efeitos dos fármacos , Masculino , RNA Mensageiro/análise , Ratos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Triglicerídeos/sangueRESUMO
Lupin protein is capable of reducing plasma lipids in hypercholesterolemic man and animals. Whether lipid-lowering properties of lupin protein will be influenced by thermal treatment or by other nutrients has not been elucidated. In a two-factorial study, rats were fed hypercholesterolemic diets based on high amounts of carbohydrates (HC) or fat (HF), which contained either (20.4% of energy) untreated or thermally treated lupin protein (steam: 120 °C, 30 min) or casein as control protein. Lupin protein lowered plasma lipid concentrations in rats fed the HF diet but not in those fed the HC diet (P<0.05). Among rats fed the HF diet, plasma and VLDL triglyceride concentrations were lower in rats fed thermally treated (-46% and -44%, P<0.05) and untreated lupin protein (-47% and -46%, P<0.05) than in those fed casein; whereas liver triglycerides were reduced only in rats fed untreated lupin protein (P<0.05). Compared to casein, untreated lupin protein had slightly stronger cholesterol-lowering effects in plasma, LDL and HDL (-34%, -37%, -35%; P<0.05) than thermally treated lupin protein (-23%, -29%, -31%, P<0.10). In conclusion, the lipid-lowering effect of lupin protein strongly depends on composition of the basal diet, and thermal treatment is accompanied by a slight reduction of its hypocholesterolemic properties.
Assuntos
Anticolesterolemiantes/farmacologia , Proteínas Alimentares/farmacologia , Hipercolesterolemia/tratamento farmacológico , Metabolismo dos Lipídeos , Proteínas de Plantas/farmacologia , Animais , Caseínas/farmacologia , Colesterol na Dieta/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Carboidratos da Dieta/metabolismo , Lipoproteínas VLDL/sangue , Fígado/metabolismo , Masculino , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangueRESUMO
Classical lipid transporters are suggested to modulate cellular vitamin D uptake. This study investigated the vitamin D levels in serum and tissues of mice deficient in SR-B1 (Srb1-/-), CD36 (Cd36-/-) and ABC-G5/G8 (Abcg5/g8-/-) and compared them with corresponding wild-type (WT) mice. All mice received triple-deuterated vitamin D3 (vitamin D3-d3) for six weeks. All knockout mice vs. WT mice showed specific alterations in their vitamin D concentrations. Srb1-/- mice had higher levels of vitamin D3-d3 in the serum, adipose tissue, kidney and heart, whereas liver levels of vitamin D3-d3 remained unaffected. Additionally, Srb1-/- mice had lower levels of deuterated 25-hydroxyvitamin D3 (25(OH)D3-d3) in the serum, liver and kidney compared to WT mice. In contrast, Cd36-/- and WT mice did not differ in the serum and tissue levels of vitamin D3-d3, but Cd36-/- vs. WT mice were characterized by lower levels of 25(OH)D3-d3 in the serum, liver and kidney. Finally, Abcg5/g8-/- mice tended to have higher levels of vitamin D3-d3 in the serum and liver. Major alterations in Abcg5/g8-/- mice were notably higher levels of 25(OH)D3-d3 in the serum and kidney, accompanied by a higher hepatic mRNA abundance of Cyp27a1 hydroxylase. To conclude, the current data emphasize the significant role of lipid transporters in the uptake, tissue distribution and activation of vitamin D.
Assuntos
Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/sangue , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/sangue , Lipoproteínas/sangue , Receptores Depuradores Classe B/sangue , Receptores Depuradores Classe B/deficiência , Vitamina D/sangue , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/deficiência , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/deficiência , Animais , Transporte Biológico , Peso Corporal , Antígenos CD36/sangue , Antígenos CD36/deficiência , Calcifediol/sangue , Colesterol/sangue , Desidrocolesteróis/sangue , Feminino , Rim/metabolismo , Lipoproteínas/deficiência , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transaminases/sangue , Triglicerídeos/sangue , Vitamina D/farmacocinéticaRESUMO
Circulating 25-hydroxyvitamin D (25(OH)D) is regarded as the most reliable biomarker of vitamin D status. However, limited data exist concerning the suitability of 25(OH)D as an indicator of body vitamin D stores and the ability of adipose tissue to mobilize vitamin D. In the first study, in which male mice received different vitamin D3 doses for three weeks, we found strong linear response relationships between vitamin D3 intake and levels of vitamin D3 in the plasma (p < 0.001), liver (p < 0.001) and adipose tissues (p < 0.001), and strong positive correlations between plasma and tissue stores of vitamin D3 (p < 0.001). Plasma levels of 25(OH)D3 and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) showed weak or no correlations with tissue vitamin D3 stores. Data from a second study demonstrate a strong and rapid response of plasma 25(OH)D3 in vitamin D3-treated mice with a low vitamin D status. Additionally, mice fed a vitamin D-free diet showed a strong and rapid decline in vitamin D3 in the liver, whereas the decline in different adipose tissues was distinctly lower than that in the liver. To conclude, tissue stores of vitamin D3 were best reflected by plasma vitamin D3. In contrast to the liver, adipose tissues responded less sensitively to an absence of vitamin D intake.