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Exercise training modulates the gut microbiota profile and impairs inflammatory signaling pathways in obese children.
Quiroga, R, Nistal, E, Estébanez, B, Porras, D, Juárez-Fernández, M, Martínez-Flórez, S, García-Mediavilla, MV, de Paz, JA, González-Gallego, J, Sánchez-Campos, S, et al
Experimental & molecular medicine. 2020;(7):1048-1061
Abstract
Childhood obesity has reached epidemic levels and is a serious health concern associated with metabolic syndrome, nonalcoholic fatty liver disease, and gut microbiota alterations. Physical exercise is known to counteract obesity progression and modulate the gut microbiota composition. This study aims to determine the effect of a 12-week strength and endurance combined training program on gut microbiota and inflammation in obese pediatric patients. Thirty-nine obese children were assigned randomly to the control or training group. Anthropometric and biochemical parameters, muscular strength, and inflammatory signaling pathways in mononuclear cells were evaluated. Bacterial composition and functionality were determined by massive sequencing and metabolomic analysis. Exercise reduced plasma glucose levels and increased dynamic strength in the upper and lower extremities compared with the obese control group. Metagenomic analysis revealed a bacterial composition associated with obesity, showing changes at the phylum, class, and genus levels. Exercise counteracted this profile, significantly reducing the Proteobacteria phylum and Gammaproteobacteria class. Moreover, physical activity tended to increase some genera, such as Blautia, Dialister, and Roseburia, leading to a microbiota profile similar to that of healthy children. Metabolomic analysis revealed changes in short-chain fatty acids, branched-chain amino acids, and several sugars in response to exercise, in correlation with a specific microbiota profile. Finally, the training protocol significantly inhibited the activation of the obesity-associated NLRP3 signaling pathway. Our data suggest the existence of an obesity-related deleterious microbiota profile that is positively modified by physical activity intervention. Exercise training could be considered an efficient nonpharmacological therapy, reducing inflammatory signaling pathways induced by obesity in children via microbiota modulation.
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Evaluation of the effects of a standardized aqueous extract of Phyllanthus emblica fruits on endothelial dysfunction, oxidative stress, systemic inflammation and lipid profile in subjects with metabolic syndrome: a randomised, double blind, placebo controlled clinical study.
Usharani, P, Merugu, PL, Nutalapati, C
BMC complementary and alternative medicine. 2019;(1):97
Abstract
BACKGROUND Endothelial dysfunction (ED) has been observed in individuals with metabolic syndrome (MetS) and contributes to the initiation and progression of atherosclerosis. The primary management of MetS involves lifestyle modifications and treatment of its individual components with drugs all of which have side effects. Thus, it would be of advantageous if natural products would be used as adjuncts or substitutes for conventional drugs. The aim of the present study was to evaluate the effect of standardized aqueous extract of fruits of Phyllanthus emblica (P. emblica) 250 mg and 500 mg twice daily on ED, oxidative stress, systemic inflammation and lipid profile in subjects with MetS. METHODS In this randomised, double-blind, placebo-controlled clinical study endothelial function was measured by calculating reflection index (RI) using digital plethysmograph. Oxidative stress biomarkers used were nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA). Systemic inflammation was measured by determining high sensitivity C-reactive protein (hsCRP) and dyslipidemia by lipid profile. ANOVA, paired and unpaired t-test were used. P-value < 0.05 was considered statistically significant. RESULTS Out of 65 screened subjects all 59 enrolled completed the study. P. emblica aqueous extract (PEE), 250 mg and 500 mg twice daily dosing, showed significant reduction in mean RI, measure of endothelial function, at 8 and 12 weeks (p < 0.001) compared to baseline and placebo. Significant mean % change was seen in oxidative stress biomarkers, NO (+ 41.89%, + 50.7%), GSH (+ 24.31%, + 53.22%) and MDA (- 21.02%, - 31.44%), and systemic inflammation biomarker, hsCRP (- 39.68%, - 53.77%) (p < 0.001) at 12 weeks with 250 mg and 500 mg twice daily dosage respectively. Significant mean % change was also seen at 12 weeks with TC (- 7.71%, - 11.11%), HDL-C (+ 7.33% + 22.16%, p < 0.05), LDL-C (- 11.39%, - 21.8%) and TG (- 9.81%, - 19.22%) respectively with 250 mg and 500 mg twice daily (p < 0.001). PEE 500 mg twice daily was significantly more efficacious than the 250 mg twice daily and placebo. No participant discontinued the study because of adverse events. CONCLUSIONS P.emblica aqueous extract significantly improved endothelial function, oxidative stress, systemic inflammation and lipid profile at both dosages tested, but especially at 500 mg twice daily. Thus, this product may be used as an adjunct to conventional therapy (lifestyle modification and pharmacological intervention) in the management of metabolic syndrome. TRIAL REGISTRATION This study was registered with Clinical Trials Registry - India (CTRI) with the registration number of CTRI/2017/09/009606 . The study was registered retrospectively on 4th September 2017.
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[Effect of Qingshen Granules on inflammation/hepcidin axis and iron metabolism in patients with renal anemia: a single-center, randomized controlled trial].
Zhang, L, Wang, Y, Jin, H, Wang, D, Wei, L, Ren, K, Mao, Y
Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 2019;(10):1155-1159
Abstract
OBJECTIVE To evaluate the therapeutic effect of Qingshen Granules on renal anemia in patients with damp-heat syndrome and explore the mechanisms in light of inflammation/hepcidin axis and iron metabolism. METHODS Sixty patients with renal anemia and dampness-heat syndrome were randomized into control group (n=30) and treatment group (n=30). All the patients were given routine treatment, and the patients in the treatment group received additional treatment with Qingshen Granules (3 times a day). After 12 weeks of treatments, the patients were examined for changes in the integral value of TCM syndrome, serum creatinine (Scr), glomerular filtration rate (eGFR), hemoglobin (HGB), hematocrit (HCT), red blood cell (RBC) count, interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), ferritin, growth differentiation factor-15 (GDF-15), serum iron (SI), total iron binding capacity (TIBC), transferrin saturation (TAST), soluble transferrin receptor (sTfR) and ferritin levels. RESULTS After the treatment, the scores of TCM syndrome were significantly improved in the treatment group and were better than those in the control group (P=0.000). Scr and eGFR were improved in both groups after the treatment. The levels of HGB, HCT and RBC were all improved in the two groups after treatment, and the improvements were more obvious in the treatment group (P=0.002, 0.002, and 0.017, respectively). The levels of IL-6, hs-CRP, hepcidine and GDF-15 were all lowered in the two groups after the treatment, and they were all significantly lower in the treatment group than in the control group (all P=0.000). The treatments increased the levels of SI and TAST in both of the groups, and compared with those in control group, the levels of TIBC, sTfR and ferritin were significantly lowered in the treatment group after the 12-week treatment (P=0.000). CONCLUSIONS Qingshen granules can effectively improve renal anemia in patients with damp-heat syndrome possibly by improving iron metabolism through alleviation of inflammation and reduction of hepcidine level.
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Evaluation of Agraz Consumption on Adipocytokines, Inflammation, and Oxidative Stress Markers in Women with Metabolic Syndrome.
Espinosa-Moncada, J, Marín-Echeverri, C, Galvis-Pérez, Y, Ciro-Gómez, G, Aristizábal, JC, Blesso, CN, Fernandez, ML, Barona-Acevedo, J
Nutrients. 2018;(11)
Abstract
Metabolic syndrome (MetS) is characterized by increased oxidative stress and a pro-inflammatory state. Vaccinium meridionale Swartz (known as "agraz") is a berry rich in polyphenolic compounds with demonstrated antioxidant activity and anti-inflammatory effects in preclinical studies. The aim of this study was to evaluate the effects of agraz consumption on inflammatory and oxidative stress markers in women with MetS. Forty women with MetS (47 ± 9 years) were randomly assigned to consume daily either 200 mL of agraz nectar or placebo over four weeks in a double-blind, cross-over design study, separated by a 4-week washout period. Metabolic and inflammatory markers in serum and antioxidant/oxidative stress markers in serum and urine were assessed at the end of each period. Serum antioxidant capacity measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method was significantly higher (p = 0.028), while urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was lower (p = 0.041) after agraz consumption, compared to placebo. In conclusion, consumption of agraz during four weeks increased serum antioxidant capacity and decreased a marker of DNA oxidative damage in women with MetS, compared to placebo. These results suggest that agraz consumption may play a protective role in patients with MetS.
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Effect of long term vitamin D supplementation on biomarkers of inflammation in Latino and African-American subjects with pre-diabetes and hypovitaminosis D.
Sinha-Hikim, I, Duran, P, Shen, R, Lee, M, Friedman, TC, Davidson, MB
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2015;(4):280-3
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Low vitamin D levels are associated with minority subjects, the metabolic syndrome, and inflammation. The effect of vitamin D supplementation on markers of inflammation has not been well studied. The aim of the study was to evaluate the effects of high doses of vitamin D supplementation for 1 year on serum biomarkers of inflammation in Latino and African-American subjects with pre-diabetes and hypovitaminosis D. Latino (n=69) and African-American (n=11) subjects who had both pre-diabetes and hypovitaminosis D with a mean age of 52.0 years, a BMI of 32.7 kg/m(2), and 70% of whom were females, were randomized to receive weekly doses (mean±SD) of vitamin D (85 300 IU±16 000) or placebo oil for 1 year. Serum levels of interleukin-6, tumor necrosis factor, highly sensitive C-reactive protein), plasminogen activator inhibitor 1, and insulin-like growth factor-1 were measured at baseline, 6, and 12 months. Serum 25-OH vitamin D levels of 22 ng/ml at baseline quickly rose to nearly 70 ng/ml in subjects receiving vitamin D and did not change in the placebo group. Two-way repeated measures ANOVA showed no differences between the 2 groups in any of the 5 selected parameters. High dose vitamin D supplementation for 1 year in minority subjects with pre-diabetes and hypovitaminosis D failed to affect serum biomarkers of inflammation.Clinical trial reg. no.: NCT00876928, clinicaltrials.gov.
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Dairy attentuates oxidative and inflammatory stress in metabolic syndrome.
Stancliffe, RA, Thorpe, T, Zemel, MB
The American journal of clinical nutrition. 2011;(2):422-30
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BACKGROUND Oxidative and inflammatory stress are elevated in obesity and are further augmented in metabolic syndrome. We showed previously that dairy components suppress the adipocyte- and macrophage-mediated generation of reactive oxygen species and inflammatory cytokines and systemic oxidative and inflammatory biomarkers in obesity. OBJECTIVE The objective of this study was to determine the early (7 d) and sustained (4 and 12 wk) effects of adequate-dairy (AD) compared with low-dairy (LD) diets in subjects with metabolic syndrome. DESIGN Forty overweight and obese adults with metabolic syndrome were randomly assigned to receive AD (3.5 daily servings) or LD (<0.5 daily servings) weight-maintenance diets for 12 wk. Oxidative and inflammatory biomarkers were assessed at 0, 1, 4, and 12 wk as primary outcomes; body weight and composition were measured at 0, 4, and 12 wk as secondary outcomes. RESULTS AD decreased malondialdehyde and oxidized LDL at 7 d (35% and 11%, respectively; P < 0.01), with further decreases by 12 wk. Inflammatory markers were suppressed with intake of AD, with decreases in tumor necrosis factor-α at 7 d and further reductions through 12 wk (35%; P < 0.05); decreases in interleukin-6 (21%; P < 0.02) and monocyte chemoattractant protein 1 (14% decrease at 4 wk, 24% decrease at 12 wk; P < 0.05); and a corresponding 55% increase in adiponectin at 12 wk (P < 0.01). LD exerted no effect on oxidative or inflammatory markers. Diet had no effect on body weight; however, AD significantly reduced waist circumference and trunk fat (P < 0.01 for both), and LD exerted no effect. CONCLUSION An increase in dairy intake attenuates oxidative and inflammatory stress in metabolic syndrome. This trial was registered at clinicaltrials.gov as NCT01266330.
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Effects of high adherence to mediterranean or low-fat diets in medicated secondary prevention patients.
Thomazella, MC, Góes, MF, Andrade, CR, Debbas, V, Barbeiro, DF, Correia, RL, Marie, SK, Cardounel, AJ, daLuz, PL, Laurindo, FR
The American journal of cardiology. 2011;(11):1523-9
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Although the Mediterranean diet (MD) and the low-fat Therapeutic Lifestyle Changes Diet (TLCD) promote equivalent increases in event-free survival in secondary coronary prevention, possible mechanisms of such complete dietary patterns in these patients, usually medicated, are unclear. The aim of this study was to investigate the effects of the MD versus the TLCD in markers of endothelial function, oxidative stress, and inflammation after acute coronary syndromes. Comparison was made between 3 months of the MD (n = 21; rich in whole grains, vegetables, fruits, nuts, and olive oil, plus red wine) and the TLCD (n = 19; plus phytosterols 2 g/day) in a highly homogenous population of stable patients who experienced coronary events in the previous 2 years (aged 45 to 65 years, all men) allocated to each diet under a strategy designed to optimize adherence, documented as >90%. Baseline demographics, body mass index and clinical data, and use of statins and other drugs were similar between groups. The MD and TLCD promoted similar decreases in body mass index and blood pressure (p ≤0.001) and particularly in plasma asymmetric dimethylarginine levels (p = 0.02) and l-arginine/asymmetric dimethylarginine ratios (p = 0.01). The 2 diets did not further enhance flow-mediated brachial artery dilation compared to baseline (4.4 ± 4.0%). Compared to the TLCD, the MD promoted decreases in blood leukocyte count (p = 0.025) and increases in high-density lipoprotein levels (p = 0.053) and baseline brachial artery diameter. Compared to the MD, the TLCD decreased low-density lipoprotein and oxidized low-density lipoprotein plasma levels, although the ratio of oxidized to total low-density lipoprotein remained unaltered. Glucose, high-sensitivity C-reactive protein, triglycerides, myeloperoxidase, intercellular adhesion molecular, vascular cell adhesion molecule, and glutathione serum and plasma levels remained unchanged with either diet. In conclusion, medicated secondary prevention patients show evident although small responses to the MD and the TLCD, with improved markers of redox homeostasis and metabolic effects potentially related to atheroprotection.
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Nutrition education guided by Dietary Guidelines for Chinese Residents on metabolic syndrome characteristics, adipokines and inflammatory markers.
Zhang, SX, Guo, HW, Wan, WT, Xue, K
Asia Pacific journal of clinical nutrition. 2011;(1):77-86
Abstract
OBJECTIVE The objective of this study was to test whether "Dietary Guidelines for Chinese Residents" have beneficial effects on anthropometric and metabolic variables, adipokines and inflammatory markers in metabolic syndrome patients. METHODS AND PROCEDURES A multi-stage sampling method was applied to select metabolic syndrome patients in two districts of Shanghai. Two hundred and seventy-two metabolic syndrome patients were divided into control and intervention groups according to their district. Nutrition education guided by "Dietary Guidelines for Chinese Residents" was performed in the intervention group for one year. RESULTS Nutrition-related knowledge, attitudes and behavior were improved in the intervention group. Potassium intake and food to total energy ratio for grain, vegetable and fruit increased while sodium intake as well as fat to total energy ratio decreased in the intervention group compared to the control group (p<0.05). Correspondently, the intervention group significantly improved its waist circumference, waist to hip ratio, high-density lipoprotein cholesterol, adiponectin, leptin and tumor necrosis factor-α compared to the control group (p<0.05). Waist circumference changes from baseline to end of the study in the intervention and the control groups were -3.9±0.3 and -2.3±0.4 cm respectively. There was a significant difference between the two groups (p=0.004). Means of waist circumference, waist to hip ratio, leptin and tumor necrosis factor-α were lower, and high density lipoprotein-cholesterol was higher in the intervention group than the control group (p<0.05). CONCLUSION This study confirmed "Dietary Guidelines for Chinese Residents" had beneficial effects on anthropometric, lipids, adipokines and inflammatory markers in metabolic syndrome patients.
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High-dose isoflavones do not improve metabolic and inflammatory parameters in androgen-deprived men with prostate cancer.
Napora, JK, Short, RG, Muller, DC, Carlson, OD, Odetunde, JO, Xu, X, Carducci, M, Travison, TG, Maggio, M, Egan, JM, et al
Journal of andrology. 2011;(1):40-8
Abstract
The profound hypogonadism that occurs with androgen deprivation therapy (ADT) for prostate cancer (PCa) results in complications such as diabetes and metabolic syndrome that predispose to cardiovascular disease. Because phytoestrogens have been associated with an improvement in metabolic parameters, we evaluated their role in men undergoing ADT. Our objective was to evaluate the effects of high-dose isoflavones on metabolic and inflammatory parameters in men undergoing ADT. This was a randomized, double-blind, placebo-controlled, 12-week pilot study. Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). The study was conducted at a tertiary care center in the United States. Thirty-three men (isoflavones = 17, placebo = 16) undergoing ADT for PCa completed this pilot study. Mean age in the 2 groups was 69 years and the majority of men were Caucasians. Mean duration of ADT in both groups was approximately 2 years (P = .70). The 2 groups were well matched at baseline. After 12 weeks of intervention, there was no significant difference in either metabolic or inflammatory parameters between the 2 groups. We found that high-dose isoflavones over a course of 12 weeks do not improve metabolic or inflammatory parameters in androgen-deprived men.
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Bioprocessing of wheat bran in whole wheat bread increases the bioavailability of phenolic acids in men and exerts antiinflammatory effects ex vivo.
Mateo Anson, N, Aura, AM, Selinheimo, E, Mattila, I, Poutanen, K, van den Berg, R, Havenaar, R, Bast, A, Haenen, GR
The Journal of nutrition. 2011;(1):137-43
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Whole grain consumption has been linked to a lower risk of metabolic syndrome, which is normally associated with a low-grade chronic inflammation. The benefits of whole grain are in part related to the inclusion of the bran, rich in phenolic acids and fiber. However, the phenols are poorly bioaccessible from the cereal matrix. The aim of the present study was to investigate the effect of bioprocessing of the bran in whole wheat bread on the bioavailability of phenolic acids, the postprandial plasma antioxidant capacity, and ex vivo antiinflammatory properties. After consumption of a low phenolic acid diet for 3 d and overnight fasting, 8 healthy men consumed 300 g of whole wheat bread containing native bran (control bread) or bioprocessed bran (bioprocessed bread) in a cross-over design. Urine and blood samples were collected for 24 h to analyze the phenolic acids and metabolites. Trolox equivalent antioxidant capacity was measured in plasma. Cytokines were measured in blood after ex vivo stimulation with LPS. The bioavailabilities of ferulic acid, vanillic acid, sinapic acid, and 3,4-dimethoxybenzoic acid from the bioprocessed bread were 2- to 3-fold those from the control bread. Phenylpropionic acid and 3-hydroxyphenylpropionic acid were the main colonic metabolites of the nonbioaccessible phenols. The ratios of pro-:antiinflammatory cytokines were significantly lower in LPS-stimulated blood after the consumption of the bioprocessed bread. In conclusion, bioprocessing can remarkably increase the bioavailability of phenolic acids and their circulating metabolites, compounds which have immunomodulatory effects ex vivo.