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A Comprehensive, Multidisciplinary, Personalized, Lifestyle Intervention Program Is Associated with Increased Leukocyte Telomere Length in Children and Adolescents with Overweight and Obesity.
Paltoglou, G, Raftopoulou, C, Nicolaides, NC, Genitsaridi, SM, Karampatsou, SI, Papadopoulou, M, Kassari, P, Charmandari, E
Nutrients. 2021;(8)
Abstract
Leucocyte telomere length (LTL) is a robust marker of biological aging and is associated with obesity and cardiometabolic risk factors in childhood and adolescence. We investigated the effect of a structured, comprehensive, multidisciplinary, personalized, lifestyle intervention program of healthy diet and physical exercise on LTL in 508 children and adolescents (239 males, 269 females; 282 prepubertal, 226 pubertal), aged 10.14 ± 0.13 years. Participants were classified as obese (n = 267, 52.6%), overweight (n = 174, 34.2%), or of normal BMI (n = 67, 13.2%) according to the International Obesity Task Force (IOTF) cutoff points and were studied prospectively for one year. We demonstrated that LTL increased significantly after 1 year of the lifestyle interventions, irrespective of gender, pubertal status, or body mass index (BMI). Waist circumference was the best negative predictor of LTL at initial assessment. The implementation of the lifestyle interventions also resulted in a significant improvement in clinical (BMI, BMI z-score and waist to height ratio) and body composition indices of obesity, inflammatory markers, hepatic enzymes, glycated hemoglobin (HbA1C), quantitative insulin sensitivity check index (QUICKI), and lipid profile in all participants. These findings indicate that the increased LTL may be associated with a more favorable metabolic profile and decreased morbidity later in life.
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Strong increase of leukocyte apha-galactosidase A activity in two male patients with Fabry disease following oral chaperone therapy.
Lamari, F, Mauhin, W, Koraichi, F, Khrouf, W, Bordet, C, London, J, Lidove, O, Charron, P
Molecular genetics & genomic medicine. 2019;(9):e894
Abstract
BACKGROUND Fabry disease (OMIM 301500) is an X-linked disorder caused by alpha-galactosidase A (α-Gal A) deficiency. The administration of a pharmacologic chaperone (migalastat) in Fabry patients with amenable mutations has been reported to improve or stabilize organ damages and reduce lyso-Gb3 plasma level. An increase of α-Gal A activity has been observed in vitro in cells expressing amenable GLA mutations when incubated with migalastat. The impact of the drug on α-Gal A in vivo activity has been poorly studied. METHODS We conducted a retrospective analysis of two unrelated male Fabry patients with p.Asn215Ser (p.N215S) variant. RESULTS We report the important increase of α-Gal A activity in blood leukocytes reaching normal ranges of activity after about 1 year of treatment with migalastat. Cardiac parameters improved or stabilized with the treatment. CONCLUSION We confirm in vivo the effects of migalastat that have been observed in N215S carriers in vitro. The increase of α-Gal A activity may be the strongest marker for biochemical efficacy. The normalization of enzyme activity could become the new therapeutic target to achieve.
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Expression of inflammation-related miRNAs in white blood cells from subjects with metabolic syndrome after 8 wk of following a Mediterranean diet-based weight loss program.
Marques-Rocha, JL, Milagro, FI, Mansego, ML, Zulet, MA, Bressan, J, Martínez, JA
Nutrition (Burbank, Los Angeles County, Calif.). 2016;(1):48-55
Abstract
OBJECTIVES The aim of this study was to evaluate the influence of a dietary strategy for weight loss (the RESMENA [reduction of metabolic syndrome in Navarra, Spain] diet) on the expression of inflammation-related microRNAS (miRNAs) and genes in white blood cells (WBC) from individuals with metabolic syndrome (MetS). METHODS The clinical, anthropometric, and biochemical characteristics of 40 individuals with MetS (20 men and 20 women; age: 48.84 ± 10.02 y; body mass index: 35.41 ± 4.42 kg/m(2)) were evaluated before and after an 8-wk hypocaloric diet based on the Mediterranean dietary pattern. Nutrient intake was assessed with a food frequency questionnaire and 48-h weighed food records. Total RNA was isolated from WBC and the expression of some inflammation-related miRNAs and mRNAs (IL-6, TNF-α, ICAM-1, IL-18, SERPINE1, VCAM-1, GAPDH) was assessed by quantitative polymerase chain reaction. RESULTS The RESMENA nutritional intervention improved most anthropometric and biochemical features. The expression of miR-155-3p was decreased in WBC, whereas Let-7b was strongly upregulated as a consequence of the dietary treatment. However, they were not correlated with the expression of the proinflammatory genes in the same cells. The changes in the expression of let-7b, miR-125b, miR-130a, miR-132-3p, and miR-422b were significantly associated with changes in diet quality when assessed by the Healthy Eating Index. Moreover, low consumption of lipids and saturated fat (g/d) were associated with higher expression of let-7b after the nutritional intervention. CONCLUSIONS The Mediterranean-based nutritional intervention was able to induce changes in the expression of let-7b and miR-155-3p in WBC from patients with MetS after 8 wk. Moreover, the quality of the diet has an important effect on the miRNAs expression changes. These results should be highlighted because these miRNAs have been associated with inflammatory gene regulation and important human diseases.
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Diagnostic performance of 18F-FDG-labeled white blood cell PET/CT for cyst infection in patients with autosomal dominant polycystic kidney disease: a prospective study.
Kwon, HW, Lee, HY, Hwang, YH, Park, HC, Ahn, C, Kang, KW
Nuclear medicine communications. 2016;(5):493-8
Abstract
OBJECTIVES Cyst infection (CI) is a common problem in patients with autosomal dominant polycystic kidney disease (ADPKD) and the accurate detection of infected cysts is very important. We evaluated the diagnostic performance of fluorine-18 fluorodeoxyglucose-labeled white blood cell (WBC) PET/computed tomography (CT) for detection of infected cysts in patients with ADPKD. PATIENTS AND METHODS Seventeen patients with ADPKD (male : female, 6 : 11; age, 53±9 years) and suspected CI were enrolled in this prospective study. Patients were classified as having definite/probable/possible CI. All patients underwent WBC PET/CT within 2 days of starting antibiotic treatment. The degree of WBC accumulation was evaluated qualitatively by nuclear medicine physicians. The diagnostic performance of WBC PET/CT was evaluated by sensitivity, specificity, positive predictive values, and negative predictive values. These values were compared with those generated from CT scans and MRI. RESULTS Seven patients were classified as having renal CI (definite 6, probable 1). In this group, WBC PET/CT showed six positive findings and one equivocal finding. Seven patients were diagnosed with possible infection. In this group, WBC PET/CT showed six negative findings and one indeterminate finding. The diagnostic performance of WBC PET/CT showed advantages over CT or MRI scans (sensitivity 85.7%, specificity 87.5%, positive predictive value 85.7%, negative predictive value 87.5%). CONCLUSION This prospective study shows that WBC PET/CT can provide an accurate diagnosis of CI in patients with ADPKD.
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Dietary supplementation with green tea extract promotes enhanced human leukocyte activity.
Lowe, GM, Gana, K, Rahman, K
Journal of complementary & integrative medicine. 2015;(4):277-82
Abstract
BACKGROUND Leukocytes play a vital role in the host defence and inflammatory systems, the latter being responsible for the pathogenesis of a wide spectrum of acute and chronic diseases. Green tea is a popular beverage, which is consumed worldwide and its active ingredients are epicatechin derivatives, which possess distinct anti-inflammatory properties. The purpose of this study was to investigate if a green tea extract could enhance leukocyte function in humans. METHODS Volunteers were asked to take 300 mg of the green tea extract daily for 14 days and the capacity of circulating leukocytes to release both myeloperoxidase and lactoferrin was assessed. Whole blood from volunteers was stimulated with the bacterial peptide Formyl-Methionine-Leucine-Phenylalanine (fMet-Leu-Phe). Myeloperoxidase an enzyme that converts hydrogen peroxide to hypochlorous acid and is stored and secreted from the granules of neutrophils and monocytes and was measured as well as lactoferrin which is an iron-binding protein stored and secreted from the neutrophils. In conjunction the antioxidant capacity of the blood of the volunteers was also determined using a chemiluminescence method that measures the capacity of plasma to scavenge superoxide. RESULTS After 14 days of treatment there was a significant increase in the release of myeloperoxidase and lactoferrin when whole blood was stimulated with fMet-Leu-Phe (p<0.05), which activates a number of leukocytes including mature neutrophils and monocytes. This was mirrored by a significant increase in the total antioxidant status after 14 days of green tea ingestion (p0.05). After the "wash-out" period of 4 weeks, all parameters were consistent with those observed at the start of the trial (day 0). Treatment with the green tea extract also caused a slight but non-significant decrease in the number of circulating leukocytes, but the counts remained within published "normal" ranges for healthy human adults. CONCLUSIONS This study indicates that a green tea extract when taken as a dietary supplement for 14 days can increase the leukocyte activity and the total plasma antioxidant status and may have role to play in the prevention of inflammatory disease.
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Insulin resistance and inflammation predict kinetic body weight changes in response to dietary weight loss and maintenance in overweight and obese subjects by using a Bayesian network approach.
Kong, LC, Wuillemin, PH, Bastard, JP, Sokolovska, N, Gougis, S, Fellahi, S, Darakhshan, F, Bonnefont-Rousselot, D, Bittar, R, Doré, J, et al
The American journal of clinical nutrition. 2013;(6):1385-94
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Abstract
BACKGROUND The ability to identify obese subjects who will lose weight in response to energy restriction is an important strategy in obesity treatment. OBJECTIVE We aimed to identify obese subjects who would lose weight and maintain weight loss through 6 wk of energy restriction and 6 wk of weight maintenance. DESIGN Fifty obese or overweight subjects underwent a 6-wk energy-restricted, high-protein diet followed by another 6 wk of weight maintenance. Network modeling by using combined biological, gut microbiota, and environmental factors was performed to identify predictors of weight trajectories. RESULTS On the basis of body weight trajectories, 3 subject clusters were identified. Clusters A and B lost more weight during energy restriction. During the stabilization phase, cluster A continued to lose weight, whereas cluster B remained stable. Cluster C lost less and rapidly regained weight during the stabilization period. At baseline, cluster C had the highest plasma insulin, interleukin (IL)-6, adipose tissue inflammation (HAM56+ cells), and Lactobacillus/Leuconostoc/Pediococcus numbers in fecal samples. Weight regain after energy restriction correlated positively with insulin resistance (homeostasis model assessment of insulin resistance: r = 0.5, P = 0.0002) and inflammatory markers (IL-6; r = 0.43, P = 0.002) at baseline. The Bayesian network identified plasma insulin, IL-6, leukocyte number, and adipose tissue (HAM56) at baseline as predictors that were sufficient to characterize the 3 clusters. The prediction accuracy reached 75.5%. CONCLUSION The resistance to weight loss and proneness to weight regain could be predicted by the combination of high plasma insulin and inflammatory markers before dietary intervention.
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Rho-kinase activation in patients with heart failure.
Do e, Z, Fukumoto, Y, Sugimura, K, Miura, Y, Tatebe, S, Yamamoto, S, Aoki, T, Nochioka, K, Nergui, S, Yaoita, N, et al
Circulation journal : official journal of the Japanese Circulation Society. 2013;(10):2542-50
Abstract
BACKGROUND Heart failure (HF) is a complex clinical syndrome, resulting from structural and/or functional cardiac disease. The aim of this study was to determine whether the activity of Rho-kinase, which has been identified as an important therapeutic target of cardiovascular disease, is enhanced in HF patients. METHODS AND RESULTS Total and phosphorylated forms of myosin binding subunit (t-MBS and p-MBS), a substrate of Rho-kinase, were measured on western blotting in circulating leukocytes, and the p-MBS/t-MBS ratio was defined as an index of systemic Rho-kinase activity. First, during the time-course of acute HF (n=12), Rho-kinase activity was significantly elevated in the acute phase compared to the chronic phase (1.19 ± 0.06 vs. 0.97 ± 0.04, P<0.05). Next, Rho-kinase activity was examined in 30 controls and 130 chronic HF patients (cardiomyopathy, n=57; valvular heart disease, n=35; ischemic heart disease [IHD], n=33; and others, n=5). As compared with the controls, Rho-kinase activity was significantly elevated in the total HF group (1.14 ± 0.02 vs. 0.77 ± 0.05, P<0.0001) and in each underlying heart disease (P<0.05 each). Importantly, in the high-risk non-IHD group, Rho-kinase activity was significantly associated with plasma brain nutriuretic peptide level. Finally, p-MBS was expressed in myocardial biopsy samples (immunohistochemistry) in chronic HF patients (n=36), independent of Rho-kinase activity in leukocytes. CONCLUSIONS Rho-kinase is activated in HF patients, suggesting that it could be a new therapeutic target of the disorder.
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Effects of soybean peptide on immune function, brain function, and neurochemistry in healthy volunteers.
Yimit, D, Hoxur, P, Amat, N, Uchikawa, K, Yamaguchi, N
Nutrition (Burbank, Los Angeles County, Calif.). 2012;(2):154-9
Abstract
OBJECTIVE Soybeans, an excellent source of dietary peptides, have beneficial effects on health. We investigated the effect of the soybean peptide on immune function, brain function, and neurochemistry in healthy volunteers. METHODS Near-infrared spectroscopy (NIRS) was used to analyze brain cerebral blood flow. The A and DA levels in the serum were analyzed by ELISA kit. The total number of leukocytes was recorded with a standard counter. Flow cytometry was used to assess lymphocyte subset levels. RESULTS Cell numbers were upregulated in the group that had fewer leukocytes but downregulated in the group with more leukocytes. For the lymphocyte-rich type, lymphocyte counts tended to decrease, accompanied by an increase in granulocyte numbers. For the granulocyte-rich type, granulocyte counts tended to increase, but lymphocyte counts also increased. The numbers of CD11b(+) cells and CD56(+) cells increased significantly. Soybean peptide decreased the adrenalin level in plasma but increased the level of dopamine. Near-infrared spectroscopy showed significant increases in the amplitudes of θ, α-2, and β-L frequency bands after the ingestion of peptides. CONCLUSION Soybean peptides can modulate cellular immune systems, regulate neurotransmitters, and boost brain function.
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Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.
Reinius, LE, Acevedo, N, Joerink, M, Pershagen, G, Dahlén, SE, Greco, D, Söderhäll, C, Scheynius, A, Kere, J
PloS one. 2012;(7):e41361
Abstract
Methylation of cytosines at CpG sites is a common epigenetic DNA modification that can be measured by a large number of methods, now even in a genome-wide manner for hundreds of thousands of sites. The application of DNA methylation analysis is becoming widely popular in complex disorders, for example, to understand part of the "missing heritability". The DNA samples most readily available for methylation studies are derived from whole blood. However, blood consists of many functionally and developmentally distinct cell populations in varying proportions. We studied whether such variation might affect the interpretation of methylation studies based on whole blood DNA. We found in healthy male blood donors there is important variation in the methylation profiles of whole blood, mononuclear cells, granulocytes, and cells from seven selected purified lineages. CpG methylation between mononuclear cells and granulocytes differed for 22% of the 8252 probes covering the selected 343 genes implicated in immune-related disorders by genome-wide association studies, and at least one probe was differentially methylated for 85% of the genes, indicating that whole blood methylation results might be unintelligible. For individual genes, even if the overall methylation patterns might appear similar, a few CpG sites in the regulatory regions may have opposite methylation patterns (i.e., hypo/hyper) in the main blood cell types. We conclude that interpretation of whole blood methylation profiles should be performed with great caution and for any differences implicated in a disorder, the differences resulting from varying proportions of white blood cell types should be considered.
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Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans.
Friebe, D, Neef, M, Kratzsch, J, Erbs, S, Dittrich, K, Garten, A, Petzold-Quinque, S, Blüher, S, Reinehr, T, Stumvoll, M, et al
Diabetologia. 2011;(5):1200-11
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Abstract
AIMS/HYPOTHESIS Nicotinamide phosphoribosyltransferase (NAMPT) is a multifunctional protein potentially involved in obesity and glucose metabolism. We systematically studied the association between circulating NAMPT, obesity, interventions and glucose metabolism and investigated potential underlying inflammatory mechanisms. METHODS Fasting morning NAMPT serum levels were measured in cohorts of lean vs obese children, cohorts of intervention by lifestyle, exercise and bariatric surgery, and during an OGTT. In addition, mRNA expression, protein production and enzymatic activity of NAMPT were assessed from isolated leucocytes and subpopulations. RESULTS Circulating NAMPT was significantly elevated in obese compared with lean children and declined after obesity interventions concomitantly with the decline in BMI, high-sensitivity C-reactive protein (hsCrP) and leucocyte counts. Circulating NAMPT significantly correlated with glucose metabolism and cardiovascular variables in univariate analyses, but only the association with glucose response during an OGTT was independent from BMI. We therefore assessed the NAMPT dynamic following an oral glucose load and found a significant decline of NAMPT levels to 77.0 ± 0.1% as a function of time, and insulin-to-glucose ratio during an OGTT in obese insulin-resistant adolescents. Circulating NAMPT was, however, most strongly associated with leucocyte counts (r = 0.46, p < 0.001). The leucocyte count itself determined significantly and independently from BMI insulin resistance in multiple regression analyses. We systematically evaluated NAMPT expression among several tissues and found that NAMPT was predominantly expressed in leucocytes. In subsequent analyses of leucocyte subpopulations, we identified higher NAMPT protein concentrations in lysates of granulocytes and monocytes compared with lymphocytes, whereas granulocytes secreted highest amounts of NAMPT protein into cell culture supernatant fractions. We confirmed nicotinamide mononucleotide enzymatic activity of NAMPT in all lysates and supernatant fractions. In monocytes, NAMPT release was significantly stimulated by lipopolysaccharide (LPS) exposure. CONCLUSIONS Leucocytes are a major source of enzymatically active NAMPT, which may serve as a biomarker or even mediator linking obesity, inflammation and insulin resistance.