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Prospective association of physical activity and inflammatory biomarkers in older adults from the PREDIMED-Plus study with overweight or obesity and metabolic syndrome.
Fuentes, GC, Castañer, O, Warnberg, J, Subirana, I, Buil-Cosiales, P, Salas-Salvadó, J, Corella, D, Serra-Majem, L, Romaguera, D, Estruch, R, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(10):3092-3098
Abstract
BACKGROUND There is limited prospective evidence on the association between physical activity (PA) and inflammation in older adults. Our aim was to assess the associations between changes in PA and changes in the inflammatory profile in older individuals who are overweight or obese. METHODS This prospective study included 489 men and women, aged 55-75 years, from the PREDIMED-Plus trial. Levels of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), monocyte chemo-attractant protein-1 (MCP-1), C-peptide, high-sensitivity C-reactive protein (hs-CRP), leptin, and regulated on activation, normal T-cell expressed and secreted chemokine (RANTES) were obtained from fasting blood samples and a composite inflammatory score based on these biomarkers was calculated. Physical activity was measured by a validated questionnaire. All measures were taken at baseline and one-year follow-up. RESULTS Multiple linear regression models showed an association between an increase in total PA and a decrease in the inflammatory score (p = 0.012), which was particularly driven by a decrease in C-peptide (p = 0.037). Similarly, the inflammatory score decreased with increasing moderate PA (p = 0.001), and moderate-to-vigorous PA (p = 0.006). CONCLUSIONS Increases in total PA, moderate and moderate-to-vigorous PA were associated with a decrease in the inflammatory profile of obese or overweight older individuals. This finding is relevant for PA recommendations and public health strategies. CLINICAL TRIAL REGISTRY Clinical trial identifier: International Standard Randomized Controlled Trial 89898870.
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The Effects of High-Protein and High-Monounsaturated Fat Meals on Postprandial Lipids, Lipoprotein Particle Numbers, Cytokines, and Leptin Responses in Overweight/Obese Subjects.
Shah, M, Adams-Huet, B, Franklin, B, Phillips, M, Mitchell, J
Metabolic syndrome and related disorders. 2018;(3):150-158
Abstract
BACKGROUND Obesity is linked to dyslipidemia, proinflammatory state, and hyperleptinemia. The influence of high-protein (HP) versus high-monounsaturated fat (HMF) meals on postprandial lipids, lipoprotein particle numbers, cytokines, and leptin responses in overweight/obese (OW/O) subjects is unknown. METHODS Twenty-four OW/O participants consumed an HP (31.9% energy from protein) and HMF (35.2% fat and 20.7% monounsaturated fat) meal, of similar energy/carbohydrate content, in a random order. The outcome variables were assessed from blood samples collected in fasted and postprandial (3 hr) states. RESULTS Repeated measures analysis found significant (P < 0.05) meal condition by time interactions for triglycerides (TGs), very low-density lipoprotein particles (VLDLP), total high-density lipoprotein particles (T-HDLP), and the ratio of large-buoyant high-density lipoprotein 2b (LB-HDL2b) to T-HDLP, and meal effect on small-dense HDLP (SD-HDLP). Comparison of HP versus HMF condition showed significantly lower TG at 120 min [geometric mean (95% confidence interval, CI): 148 (125-175) vs. 194 (164-230) mg/dL] and 180 min [167 (138-203) vs. 230 (189-278) mg/dL] and VLDLP at 180 min [70.0 (58.2-84.3) vs. 88.0 (73.1-106) nmol/L]. HP versus HMF condition showed significantly lower LB-HDL2b/T-HDLP at 180 min [mean difference (95% CI): 0.021 (0.004-0.038)], and higher T-HDLP [671 (263-1079) nmol/L] and SD-HDLP [606 (292-920) nmol/L] at 120 min. Area under the curve was significantly lower for TG and higher for T-HDLP, SD-HDLP, and small-dense LDL III (SD-LDL III) in the HP condition. Cytokines and leptin were not different between conditions. CONCLUSION OW/O subjects had lower TG and VLDLP, but less favorable SD-LDL III, SD-HDLP, and LB-HDL2b/T-HDLP ratio responses to the HP versus HMF meals.
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Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.
Smits, LP, Kootte, RS, Levin, E, Prodan, A, Fuentes, S, Zoetendal, EG, Wang, Z, Levison, BS, Cleophas, MCP, Kemper, EM, et al
Journal of the American Heart Association. 2018;(7)
Abstract
BACKGROUND Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. METHODS AND RESULTS We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d6-choline and d3-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. CONCLUSIONS Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. CLINICAL TRIAL REGISTRATION URL: http://www.trialregister.nl. Unique identifier: NTR 4338.
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Anti-Inflammatory Effect of Crocus sativus on Serum Cytokine Levels in Subjects with Metabolic Syndrome: A Randomized, Double-Blind, Placebo- Controlled Trial.
Kermani, T, Zebarjadi, M, Mehrad-Majd, H, Mirhafez, SR, Shemshian, M, Ghasemi, F, Mohammadzadeh, E, Mousavi, SH, Norouzy, A, Moghiman, T, et al
Current clinical pharmacology. 2017;(2):122-126
Abstract
BACKGROUND/AIMS: A growing body of evidence supports an important role of inflammatory cytokines in the development and progression of the Metabolic Syndrome (MetS), which explains, at least in part, its relationship with an increased cardiovascular-risk. Several studies have reported the therapeutic-impact of crocus-sativus in a preclinical/clinical setting. Here we have explored the effects of crocus-sativus, on the serum concentrations of twelve serum cytokines in subjects with MetS in a randomized control trial. METHODS Forty four adult volunteers, who met the diagnostic-criteria of MetS, were enrolled and randomly divided into 2 groups, to receive 100 mg/day crocus-sativus for 12 weeks. 12 cytokines, including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, MCP-1, IFN-γ, EGF, and VEGF were measured using sandwich chemi-luminescence assays before/after therapy. RESULTS Individuals with MetS who received crocus-sativus had significantly (P<0.05) lower levels of total-cholesterol, low density-lipoprotein-cholesterol and triglyceride (TG), fasting-blood-sugar and hsCRP, however the serum concentration of high density-lipoprotein-cholesterol markedly enhanced after therapy (e.g., TG level reduced from 148.86±71.49 to 101.90±38.19 after therapy, P= 0.003). Moreover, we observed that treatment with Crocus-sativus affected the serumconcentrations of some pro-/anti-inflamatory cytokines. In particular, the level of VEGF was increased from 12.64 pg/mL (95% CI: 9.60-17.67) to 16.59 (95% CI: 11.33-35.98, P= 0.033. Similar results were detected for IL-6 and EGF. CONCLUSION Our findings provide a novel insight into the therapeutic effects of this therapy in MetS patients via perturbation of serum cytokines and reducing the levels of triglyceride and LDL/TC, but further studies are required in larger populations.
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Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial.
Panahi, Y, Hosseini, MS, Khalili, N, Naimi, E, Simental-Mendía, LE, Majeed, M, Sahebkar, A
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2016;:578-82
Abstract
BACKGROUND Cytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS. METHODS This study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1g/day) or a matched placebo for a period of 8 weeks. RESULTS One hundred and seventeen subjects were assigned to either curcumin (n=59) or placebo (n=58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p<0.001). In the placebo group, serum levels of TGF-β were decreased (p=0.003) but those of IL-6 (p=0.735), TNF-α (p=0.138) and MCP-1 (p=0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p<0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines. CONCLUSION Results of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.
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Inflammation's Association with Metabolic Profiles before and after a Twelve-Week Clinical Trial in Drug-Naïve Patients with Bipolar II Disorder.
Lee, SY, Chen, SL, Chang, YH, Chen, PS, Huang, SY, Tzeng, NS, Wang, YS, Wang, LJ, Lee, IH, Wang, TY, et al
PloS one. 2013;(6):e66847
Abstract
UNLABELLED Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP) and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naïve patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naïve patients (n = 117) diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI) and plasma cytokines (TNF-α, CRP, IL-6, and TGF-β) were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0%) patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (P = 1.7E-7) and triglyceride (P = 0.005) levels. Changes in plasma TGF-β1 were significantly associated with changes in BMI (P = 8.2E-6), cholesterol (P = 0.004), and triglyceride (P = 0.006) levels. However, changes in plasma TNF-α and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (P = 0.003) levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (P = 0.006) and TNF-α (P = 0.039) levels. Plasma CRP and TGF-β1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology of clinical symptoms and metabolic disturbance in BP-II. TRIAL REGISTRATION ClinicalTrials.gov NCT01188148.
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Exchanging saturated fatty acids for (n-6) polyunsaturated fatty acids in a mixed meal may decrease postprandial lipemia and markers of inflammation and endothelial activity in overweight men.
Masson, CJ, Mensink, RP
The Journal of nutrition. 2011;(5):816-21
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Abstract
Postprandial lipemia, low-grade systemic inflammation, and endothelial activity are related to metabolic disorders. It is well known that dietary fatty acid composition modulates postprandial lipemia, but information on the other metabolic risk markers is limited. We therefore studied the acute effects of a meal rich in SFA compared with those of a meal rich in (n-6) PUFA on postprandial responses in overweight men who are at an increased risk to develop the metabolic syndrome and its comorbidities. In a crossover design, the effects of 50 g butter (rich in SFA) on lipemia and markers for inflammation and endothelial activity were compared with those of 50 g sunflower oil [rich in (n-6) PUFA] during an 8-h postprandial mixed meal tolerance test in 13 overweight men. Postprandial changes in serum TG were comparable between the meals (P = 0.38), except for a reduction in the incremental area under the curve (P = 0.046) in the late postprandial phase after (n-6) PUFA (125 ± 96 mmol⋅min⋅L(-1)) compared with SFA (148 ± 98 mmol⋅min⋅L(-1)). Compared with the SFA meal, the (n-6) PUFA meal decreased plasma IL-6 (P = 0.003), TNFα (P = 0.005), soluble TNF receptors I and II (sTNFr; P = 0.024 and P < 0.001, respectively), and soluble vascular cell adhesion molecule-1 (sVCAM-1; P = 0.030) concentrations. These results indicate that exchanging SFA from butterfat for (n-6) PUFA in a mixed meal may decrease postprandial lipemia and concentrations of IL-6, TNFα, sTNFr-I and -II, and sVCAM-1 in overweight men.
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Fenofibrate reduces fasting and postprandial inflammatory responses among hypertriglyceridemia patients with the metabolic syndrome.
Rosenson, RS, Huskin, AL, Wolff, DA, Helenowski, IB, Rademaker, AW
Atherosclerosis. 2008;(2):381-8
Abstract
OBJECTIVE To examine the effects of fenofibrate (160mg/d) therapy on fasting and postprandial cytokine production in subjects with metabolic syndrome and hypertriglyceridemia. RESEARCH DESIGN AND METHODS Randomized, double-blind, controlled trial that compared the effects of 3-month therapy with placebo and fenofibrate on fasting and postprandial cytokine production in 55 subjects with metabolic syndrome and elevated fasting triglycerides (>or=1.7 and <6.78mmol/L). RESULTS Fenofibrate treatment reduced concentrations of monohydroxy fatty acids (OH-FA) by 15.5% (p=0.001), lipopolysaccharide activated monocyte chemotactic protein-1 (MCP-1/CCL2) production in fasting blood samples by 3.4% (p=0.01 vs. placebo), macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3) by 3.5% (p=0.01), and interleukin-1beta (IL-1beta) by 2.5% (p=0.04). After a standardized fat load (50kg/m(2)), OH-FA were reduced by 31.0% (p<0.0001), MCP-1/CCL2 was reduced by 5.2% (p=0.002), MIP-1alpha/CCL3 by 3.9% (p=0.007), and IL-1beta by 3.4% (p=0.02). Reductions in MCP-1/CCL2, MIP-1alpha/CCL3, and IL-1beta production correlated with changes in fasting and postprandial large very low-density lipoprotein (VLDL) (all p<0.005) and small low-density lipoprotein (LDL) particles (all p<0.05). In stepwise regression models that included age, gender, weight change, and drug assignment, large VLDL particles were associated with reductions in postprandial MCP-1/CCL2 (p=0.042), MIP-1alpha/CCL3 (p=0.003), and IL-1beta (p=0.02). CONCLUSIONS This study reports that fenofibrate reduces whole blood production of inflammatory cytokines and hepatic-synthesized inflammatory proteins, and the anti-inflammatory effects of fenofibrate therapy involve VLDL- and LDL-mediated pathways.