Publications by authors named "Jozef Ukropec"

69 Publications

Effects of Short- and Long-Term Aerobic-Strength Training and Determinants of Walking Speed in the Elderly.

Gerontology 2021 May 10:1-11. Epub 2021 May 10.

Biomedical Research Center, Institute of Experimental Endocrinology, Slovak Academy of Sciences, University Science, Park for Biomedicine, Bratislava, Slovakia.

Background/aims: Walking speed (WS) is an objective measure of physical capacity and a modifiable risk factor of morbidity and mortality in the elderly. In this study, we (i) determined effects of 3-month supervised aerobic-strength training on WS, muscle strength, and habitual physical activity; (ii) evaluated capacity of long-term (21 months) training to sustain higher WS; and (iii) identified determinants of WS in the elderly.

Methods: Volunteers (F 48/M 14, 68.4 ± 7.1 years) completed either 3-month aerobic-strength (3 × 1 h/week, n = 48) or stretching (active control, n = 14) intervention (study A). Thirty-one individuals (F 24/M 7) from study A continued in supervised aerobic-strength training (2 × 1 h/week, 21 months) and 6 (F 5/M 1) became nonexercising controls.

Results: Three-month aerobic-strength training increased preferred and maximal WS (10-m walk test, p < 0.01), muscle strength (p < 0.01) and torque (p < 0.01) at knee extension, and 24-h habitual physical activity (p < 0.001), while stretching increased only preferred WS (p < 0.03). Effect of training on maximal WS was most prominent in individuals with baseline WS between 1.85 and 2.30 m·s-1. Maximal WS measured before intervention correlated negatively with age (r = -0.339, p = 0.007), but this correlation was weakened by the intervention (r = -0.238, p = 0.06). WS progressively increased within the first 9 months of aerobic-strength training (p < 0.001) and remained elevated during 21-month intervention (p < 0.01). Cerebellar gray matter volume (MRI) was positively associated with maximal (r = 0.54; p < 0.0001) but not preferred WS and explained >26% of its variability, while age had only minor effect.

Conclusions: Supervised aerobic-strength training increased WS, strength, and dynamics of voluntary knee extension as well as habitual physical activity in older individuals. Favorable changes in WS were sustainable over the 21-month period by a lower dose of aerobic-strength training. Training effects on WS were not limited by age, and cerebellar cortex volume was the key determinant of WS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000515325DOI Listing
May 2021

Lysosomal lipoprotein processing in endothelial cells stimulates adipose tissue thermogenic adaptation.

Cell Metab 2021 Mar 22;33(3):547-564.e7. Epub 2020 Dec 22.

Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

In response to cold exposure, thermogenic adipocytes internalize large amounts of fatty acids after lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TRL) in the capillary lumen of brown adipose tissue (BAT) and white adipose tissue (WAT). Here, we show that in cold-exposed mice, vascular endothelial cells in adipose tissues endocytose substantial amounts of entire TRL particles. These lipoproteins subsequently follow the endosomal-lysosomal pathway, where they undergo lysosomal acid lipase (LAL)-mediated processing. Endothelial cell-specific LAL deficiency results in impaired thermogenic capacity as a consequence of reduced recruitment of brown and brite/beige adipocytes. Mechanistically, TRL processing by LAL induces proliferation of endothelial cells and adipocyte precursors via beta-oxidation-dependent production of reactive oxygen species, which in turn stimulates hypoxia-inducible factor-1α-dependent proliferative responses. In conclusion, this study demonstrates a physiological role for TRL particle uptake into BAT and WAT and establishes endothelial lipoprotein processing as an important determinant of adipose tissue remodeling during thermogenic adaptation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2020.12.001DOI Listing
March 2021

Clusterin is upregulated in serum and muscle tissue in idiopathic inflammatory myopathies and associates with clinical disease activity and cytokine profile.

Clin Exp Rheumatol 2020 Oct 29. Epub 2020 Oct 29.

Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Objectives: The aim of this cross-sectional study was to explore the circulating and skeletal muscle expression of clusterin (CLU) in inflammatory myopathies (IIM) and its potential implication in pathogenetic mechanisms of the disease.

Methods: A total of 85 IIM patients and 86 healthy controls (HC) were recruited. In addition, 20 IIM patients and 21 HC underwent a muscle biopsy. Circulating CLU was measured by ELISA. Serum cytokine profile of patients and HC was assessed by Cytokine 27-plex Assay. Immunohistochemical localisation of CLU was assessed in 10 IIM and 4 control muscle tissue specimens. The expression of CLU and myositis related cytokines in muscle was determined by qPCR.

Results: Serum levels of CLU were significantly increased in IIM patients compared to controls (86.2 (71.6-99.0) vs. 59.6 (52.6-68.4) μg/mL, p<0.0001) and positively correlated with myositis disease activity assessment (MYOACT) (r=0.337, p=0.008), myositis intention-to-treat activity index (MITAX) (r=0.357, p=0.004) and global disease assessment evaluated by physician (r=0.309, p=0.015). Moreover, serum CLU correlated with cytokines and chemokines involved in IIM and their combined effect on disease activity was revealed by multivariate redundancy analysis. In muscle tissue, CLU mRNA was increased in IIM patients compared to controls (p=0.032) and CLU accumulated in the cytoplasm of regenerating myofibres.

Conclusions: We suggest that the up-regulation of clusterin in circulation and skeletal muscle of IIM patients may be an inflammation and atrophy induced response of the organism intended to limit the environment, favouring further muscle damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2020

snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis.

Nature 2020 11 28;587(7832):98-102. Epub 2020 Oct 28.

Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.

Adipose tissue is usually classified on the basis of its function as white, brown or beige (brite). It is an important regulator of systemic metabolism, as shown by the fact that dysfunctional adipose tissue in obesity leads to a variety of secondary metabolic complications. In addition, adipose tissue functions as a signalling hub that regulates systemic metabolism through paracrine and endocrine signals. Here we use single-nucleus RNA-sequencing (snRNA-seq) analysis in mice and humans to characterize adipocyte heterogeneity. We identify a rare subpopulation of adipocytes in mice that increases in abundance at higher temperatures, and we show that this subpopulation regulates the activity of neighbouring adipocytes through acetate-mediated modulation of their thermogenic capacity. Human adipose tissue contains higher numbers of cells of this subpopulation, which could explain the lower thermogenic activity of human compared to mouse adipose tissue and suggests that targeting this pathway could be used to restore thermogenic activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2856-xDOI Listing
November 2020

Allelic Distribution of Genes for Apolipoprotein E and MTHFR in Patients with Alzheimer's Disease and Their Epistatic Interaction.

J Alzheimers Dis 2020 ;77(3):1095-1105

1st Department of Neurology, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia.

Background: Genetic risk factors play an important role in the pathogenesis of Alzheimer's disease (AD). However, the gene-gene interaction (epistasis) between specific allelic variants is only partially understood.

Objective: In our study, we examined the presence of the ɛ4 allele of apolipoprotein E (APOE) and the presence of C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with AD and controls. We also evaluated the epistatic interaction between MTHFR and the APOE variants.

Methods: A total of 564 patients with AD and 534 cognitively unimpaired age-matched controls were involved in the study.

Results: The presence of the ɛ4 allele of APOE increases the risk of developing AD in a dose-dependent manner (OR 32.7: homozygotes, 15.6: homozygotes + heterozygotes, 14.3: heterozygotes). The combination of genotypes also increases the risk of developing AD in a dose-dependent manner: OR 18.3 (APOE 4/X and 4/4 + CT rs1801133), OR 19.4 (APOE 4/X and 4/4 + CT rs1801133 + AC rs1801131), OR 22.4 (APOE 4/X and 4/4 + TT rs1801133), and OR 21.2 (APOE 4/X and 4/4 + CC rs1801131). Homozygotes for variant alleles of MTHFR as well as patients with AD had significantly higher levels of homocysteine than homozygotes for standard alleles or controls.

Conclusion: Homozygotes for APOE4 and carriers of APOE4 with TT genotype of rs1801133 were found to be at the highest risk of developing AD. These findings suggest that the epistatic interaction of specific gene variants can have a significant effect on the development of AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-200321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683064PMC
January 2020

Multinuclear MRS at 7T Uncovers Exercise Driven Differences in Skeletal Muscle Energy Metabolism Between Young and Seniors.

Front Physiol 2020 29;11:644. Epub 2020 Jun 29.

High Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.

Aging is associated with changes in muscle energy metabolism. Proton (H) and phosphorous (P) magnetic resonance spectroscopy (MRS) has been successfully applied for non-invasive investigation of skeletal muscle metabolism. The aim of this study was to detect differences in adenosine triphosphate (ATP) production in the aging muscle by P-MRS and to identify potential changes associated with buffer capacity of muscle carnosine by H-MRS. Fifteen young and nineteen elderly volunteers were examined. H and P-MRS spectra were acquired at high field (7T). The investigation included carnosine quantification using H-MRS and resting and dynamic P-MRS, both including saturation transfer measurements of phosphocreatine (PCr), and inorganic phosphate (Pi)-to-ATP metabolic fluxes. Elderly volunteers had higher time constant of PCr recovery (τ ) in comparison to the young volunteers. Exercise was connected with significant decrease in PCr-to-ATP flux in both groups. Moreover, PCr-to-ATP flux was significantly higher in young compared to elderly both at rest and during exercise. Similarly, an increment of Pi-to-ATP flux with exercise was found in both groups but the intergroup difference was only observed during exercise. Elderly had lower muscle carnosine concentration and lower postexercise pH. A strong increase in phosphomonoester (PME) concentration was observed with exercise in elderly, and a faster Pi:PCr kinetics was found in young volunteers compared to elderly during the recovery period. Observations of a massive increment of PME concentration together with high Pi-to-ATP flux during exercise in seniors refer to decreased ability of the muscle to meet the metabolic requirements of exercise and thus a limited ability of seniors to effectively support the exercise load.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.00644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336536PMC
June 2020

The effectiveness of two different multimodal training modes on physical performance in elderly.

Eur J Transl Myol 2020 Apr 1;30(1):8820. Epub 2020 Apr 1.

Department of Biological and Medical Sciences, Faculty of Physical Education and Sports, Comenius University, Bratislava, Slovakia.

The study compared the effect of 12-week multimodal training programme performed twice a week at the regular exercise facility (REF) with the 12-week multimodal training programme performed three times per week as a part of the research programme (EX). Additionally, the study analysed how the experimental training programme affect the physical performance of cognitive healthy and mild cognitive impaired elderly (MCI). The REF training group included 19 elderly (65.00±3.62 years). The experimental training programme combined cognitively healthy (EXH: n=16; 66.3±6.42 years) and age-matched individuals with MCI (EXMCI: n=14; 66.00±4.79 years). 10m maximal walking speed (10mMWS), Five Times Sit-to-Stand Test (FTSS), maximal and relative voluntary contraction (MVC & rel. MVC) were analysed. The REF group improved in 10mMWS (t=2.431, p=.026), the MVC (t=-3.528, p=.002) and relative MVC (t=3.553, p=.002). The EXH group improved in FTSS (t=5.210, P=.000), MVC (t=2.771, p=.018) and relative MVC (t=-3.793, p=.004). EXMCI improved in FTSS (t=2.936, p=.012) and MVC (t=-2.276, p=.040). According to results, both training programmes sufficiently improved walking speed and muscle strength in cognitively healthy elderly. Moreover, the experimental training programme improved muscle strength in MCI elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/ejtm.2019.8820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254426PMC
April 2020

Cold Exposure Distinctively Modulates Parathyroid and Thyroid Hormones in Cold-Acclimatized and Non-Acclimatized Humans.

Endocrinology 2020 07;161(7)

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.

Cold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood. We aimed to investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans. Examinations were performed before/after 15 minutes of ice-water swimming (n = 15) or 120 to 150 minutes of cold-induced nonshivering thermogenesis (NST) applied to cold-acclimatized (n = 6) or non-acclimatized (n = 11) individuals. Deep-neck brown adipose tissue (BAT) was collected from non-acclimatized patients undergoing elective neck surgery (n = 36). Seasonal variations in metabolic/hormonal parameters of ice-water swimmers were evaluated. We found that in ice-water swimmers, PTH and TSH increased and free T3, T4 decreased after a 15-minute winter swim, whereas NST-inducing cold exposure failed to regulate PTH and free T4 and lowered TSH and free T3. Ice-water swimming-induced increase in PTH correlated negatively with systemic calcium and positively with phosphorus. In non-acclimatized men, NST-inducing cold decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT volume was found across the 2 populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively with UCP1/UCP1, PPARGC1A, and DIO2 in BAT from neck surgery patients. Our data suggest that regulation of PTH and thyroid hormones during cold exposure in humans varies by cold acclimatization level and/or cold stimulus intensity. Possible role of PTH in NST is indicated by its positive relationships with whole-body metabolic preference for lipids, BAT volume, and UCP1 content.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/endocr/bqaa051DOI Listing
July 2020

Author Correction: Effect of carnosine supplementation on the plasma lipidome in overweight and obese adults: a pilot randomised controlled trial.

Sci Rep 2020 Mar 4;10(1):4384. Epub 2020 Mar 4.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-61335-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054394PMC
March 2020

Alterations in activin A-myostatin-follistatin system associate with disease activity in inflammatory myopathies.

Rheumatology (Oxford) 2020 09;59(9):2491-2501

Division of Experimental Rheumatology, Institute of Rheumatology, Prague.

Objectives: The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis.

Methods: A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-β1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR.

Results: We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = -0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls.

Conclusion: This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A-myostatin-follistatin system in muscle wasting diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/kez651DOI Listing
September 2020

Acute and regular exercise distinctly modulate serum, plasma and skeletal muscle BDNF in the elderly.

Neuropeptides 2019 Dec 29;78:101961. Epub 2019 Aug 29.

Institute of Experimental Endocrinology, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia. Electronic address:

Brain-derived neurotrophic factor (BDNF) participates in orchestrating the adaptive response to exercise. However, the importance of transient changes in circulating BDNF for eliciting whole-body and skeletal muscle exercise benefits in humans remains relatively unexplored. Here, we investigated effects of acute aerobic exercise and 3-month aerobic-strength training on serum, plasma and skeletal muscle BDNF in twenty-two sedentary older individuals (69.0 ± 8.0 yrs., 9 M/13F). BDNF response to acute exercise was additionally evaluated in young trained individuals (25.1 ± 2.1 yrs., 3 M/5F). Acute aerobic exercise transiently increased serum BDNF in sedentary (16%, p = .007) but not in trained elderly or young individuals. Resting serum or plasma BDNF was not regulated by exercise training in the elderly. However, subtle training-related changes of serum BDNF positively correlated with improvements in walking speed (R = 0.59, p = .005), muscle mass (R = 0.43, p = .04) and cognitive performance (R = 0.41, p = .05) and negatively with changes in body fat (R = -0.43, p = .04) and triglyceridemia (R = -0.53, p = .01). Individuals who increased muscle BDNF protein in response to 3-month training (responders) displayed stronger acute exercise-induced increase in serum BDNF than non-responders (p = .006). In addition, muscle BDNF protein content positively correlated with type II-to-type I muscle fiber ratio (R = 0.587, p = .008) and with the rate of post-exercise muscle ATP re-synthesis (R = 0.703, p = .005). Contrary to serum, acute aerobic exercise resulted in a decline of plasma BDNF 1 h post-exercise in both elderly-trained (-34%, p = .002) and young-trained individuals (-48%, p = .034). Acute circulating BDNF regulation by exercise was dependent on the level of physical fitness and correlated with training-induced improvements in metabolic and cognitive functions. Our observations provide an indirect evidence that distinct exercise-induced changes in serum and plasma BDNF as well as training-related increase in muscle BDNF protein, paralleled by improvements in muscle and whole-body clinical phenotypes, are involved in the coordinated adaptive response to exercise in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.npep.2019.101961DOI Listing
December 2019

Strength training as a supplemental therapy for androgen deficiency of the aging male (ADAM): study protocol for a three-arm clinical trial.

BMJ Open 2019 09 5;9(9):e025991. Epub 2019 Sep 5.

Deparment of Biological and Medical Sciences, Faculty of Physical Education and Sports, Comenius University in Bratislava, Bratislava, Slovakia

Introduction: Androgen deficiency of the ageing male is a clinical syndrome resulting from the low production of androgens (testosterone levels <6.9 nmol/L) with symptoms including decline in lean mass, muscle strength, increases in body mass and overall fat mass. The aim of the study is to examine the effect of a 12 week strength training intervention on body composition, physical function, muscle cellular and molecular and selected biochemical markers of metabolic health in hypogonadal patients.

Methods And Analysis: The study is three-group controlled 12-week experiment to assess the effect of strength training on hypogonadal patients with testosterone replacement therapy and newly diagnosed males without testosterone replacement therapy. Age matched healthy eugonadal males are also engaged in strength training. Lean mass is used to determine sample size indicating, that 22 subjects per group will be sufficient to detect intervention related changes at the power of 0.90. All outcomes are collected before the intervention (pre-intervention assessments) and after the intervention (post-intervention assessments). Clinical outcomes are body composition (lean mass, fat mass and total body mass) measured by dual-energy X-ray absorptiometry, physical functioning assessed by physical tests and psychosocial functioning. The most important haematological and biochemical parameters included are glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, testosterone, luteinizing hormone, follicle-stimulating hormone, sexhormone-binding globulin, insulin and prostate-specific antigen. Muscle cellular and molecular outcomes are muscle fibre size and regulators of muscle fibre size. Muscle cellular outcomes are measured from muscle biopsies obtained from musculus vastus lateralis.

Ethics And Dissemination: This trial is approved by Ethics Committee of the University Hospital in Bratislava, Slovakia, (ref. trial number: 127/2017) and all subjects will be fully informed on the rationale, risks and benefits of the study and sign the written informed consent prior to entering the study. Results will be published in peer-reviewed journals and presented in scientific conferences.

Trial Registration Number: NCT03282682.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-025991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731925PMC
September 2019

The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence.

Nutrients 2019 May 28;11(6). Epub 2019 May 28.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Melbourne, Victoria 3168, Australia.

Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological presence of this di-peptide and its analogues in the brain together with their ability to cross the blood-brain barrier as well as evidence from in vitro, animal, and human studies suggest carnosine as a promising therapeutic target in brain disorders. In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu11061196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627134PMC
May 2019

Distinctive Effects of Aerobic and Resistance Exercise Modes on Neurocognitive and Biochemical Changes in Individuals with Mild Cognitive Impairment.

Curr Alzheimer Res 2019 ;16(4):316-332

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Slovakia, Dubravska cesta 9, 84505 Bratislava, Slovakia.

Background: Decreased levels of the neuroprotective growth factors, low-grade inflammation, and reduced neurocognitive functions during aging are associated with neurodegenerative diseases, such as Alzheimer's disease. Physical exercise modifies these disadvantageous phenomena while a sedentary lifestyle promotes them.

Purpose: The purposes of the present study included investigating whether both aerobic and resistance exercise produce divergent effects on the neuroprotective growth factors, inflammatory cytokines, and neurocognitive performance, and further exploring whether changes in the levels of these molecular biomarkers are associated with alterations in neurocognitive performance.

Methods: Fifty-five older adults with amnestic MCI (aMCI) were recruited and randomly assigned to an aerobic exercise (AE) group, a resistance exercise (RE) group, or a control group. The assessment included neurocognitive measures [e.g., behavior and event-related potential (ERP)] during a task-switching paradigm, as well as circulating neuroprotective growth factors (e.g., BDNF, IGF-1, VEGF, and FGF-2) and inflammatory cytokine (e.g., TNF-α, IL-1β, IL-6, IL-8, and IL-15) levels at baseline and after either a 16-week aerobic or resistance exercise intervention program or a control period.

Results: Aerobic and resistance exercise could effectively partially facilitate neurocognitive performance [e.g., accuracy rates (ARs), reaction times during the heterogeneous condition, global switching cost, and ERP P3 amplitude] when the participants performed the task switching paradigm although the ERP P2 components and P3 latency could not be changed. In terms of the circulating molecular biomarkers, the 16-week exercise interventions did not change some parameters (e.g., leptin, VEGF, FGF-2, IL-1β, IL-6, and IL-8). However, the peripheral serum BDNF level was significantly increased, and the levels of insulin, TNF-α, and IL-15 levels were significantly decreased in the AE group, whereas the RE group showed significantly increased IGF-1 levels and decreased IL-15 levels. The relationships between the changes in neurocognitive performance (AR and P3 amplitudes) and the changes in the levels of neurotrophins (BDNF and IGF-1)/inflammatory cytokines (TNF-α) only approached significance.

Conclusion: These findings suggested that in older adults with aMCI, not only aerobic but also resistance exercise is effective with regard to increasing neurotrophins, reducing some inflammatory cytokines, and facilitating neurocognitive performance. However, the aerobic and resistance exercise modes likely employed divergent molecular mechanisms on neurocognitive facilitation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1567205016666190228125429DOI Listing
August 2020

Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation.

Cell Metab 2019 04 20;29(4):901-916.e8. Epub 2018 Dec 20.

Institute of Food, Nutrition, and Health, ETH Zürich, Schorenstrasse 16, Schwerzenbach 8603, Switzerland. Electronic address:

Recent research focusing on brown adipose tissue (BAT) function emphasizes its importance in systemic metabolic homeostasis. We show here that genetic and pharmacological inhibition of the mevalonate pathway leads to reduced human and mouse brown adipocyte function in vitro and impaired adipose tissue browning in vivo. A retrospective analysis of a large patient cohort suggests an inverse correlation between statin use and active BAT in humans, while we show in a prospective clinical trial that fluvastatin reduces thermogenic gene expression in human BAT. We identify geranylgeranyl pyrophosphate as the key mevalonate pathway intermediate driving adipocyte browning in vitro and in vivo, whose effects are mediated by geranylgeranyltransferases (GGTases), enzymes catalyzing geranylgeranylation of small GTP-binding proteins, thereby regulating YAP1/TAZ signaling through F-actin modulation. Conversely, adipocyte-specific ablation of GGTase I leads to impaired adipocyte browning, reduced energy expenditure, and glucose intolerance under obesogenic conditions, highlighting the importance of this pathway in modulating brown adipocyte functionality and systemic metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2018.11.017DOI Listing
April 2019

Ultralong TE In Vivo H MR Spectroscopy of Omega-3 Fatty Acids in Subcutaneous Adipose Tissue at 7 T.

J Magn Reson Imaging 2019 07 21;50(1):71-82. Epub 2018 Dec 21.

High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.

Background: Omega-3 (n-3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n-3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly.

Purpose: To detect omega-3 (n-3 CH ) and non-omega-3 (CH ) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n-3 FA content, and the n-3 FA fraction in adipose tissue in vivo.

Study Type: Prospective technical development.

Population: Three oils with different n-3 FA content and 24 healthy subjects.

Field Strength/sequence: Single-voxel MR spectroscopy (SVS) with a point-resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T.

Assessment: Knowledge about the J-coupling evolution of both CH resonances was used for the optimal detection of the n-3 CH resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis.

Statistical Tests: SVS data were compared to gas chromatography with the Pearson correlation coefficient.

Results: T relaxation times in oils were assessed as follows: CH , 65 ± 22 msec; CH , 325 ± 7 msec; and n-3 CH , 628 ± 34 msec. The n-3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029).

Data Conclusion: PRESS with ultralong-TE can detect and quantify the n-3 CH signal in vivo at 7 T.

Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71-82.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.26605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618283PMC
July 2019

BATLAS: Deconvoluting Brown Adipose Tissue.

Cell Rep 2018 10;25(3):784-797.e4

Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland. Electronic address:

Recruitment and activation of thermogenic adipocytes have received increasing attention as a strategy to improve systemic metabolic control. The analysis of brown and brite adipocytes is complicated by the complexity of adipose tissue biopsies. Here, we provide an in-depth analysis of pure brown, brite, and white adipocyte transcriptomes. By combining mouse and human transcriptome data, we identify a gene signature that can classify brown and white adipocytes in mice and men. Using a machine-learning-based cell deconvolution approach, we develop an algorithm proficient in calculating the brown adipocyte content in complex human and mouse biopsies. Applying this algorithm, we can show in a human weight loss study that brown adipose tissue (BAT) content is associated with energy expenditure and the propensity to lose weight. This online available tool can be used for in-depth characterization of complex adipose tissue samples and may support the development of therapeutic strategies to increase energy expenditure in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2018.09.044DOI Listing
October 2018

Carnosine Supplementation Improves Serum Resistin Concentrations in Overweight or Obese Otherwise Healthy Adults: A Pilot Randomized Trial.

Nutrients 2018 Sep 7;10(9). Epub 2018 Sep 7.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3168, Australia.

Adipokines play an important role in the regulation of glucose metabolism. We have previously shown that carnosine supplementation in overweight or obese non-diabetic individuals improves glucose metabolism but does not change adiponectin concentrations. However, its effect on other adipokines has not been investigated. Herein we further determined the effect of carnosine supplementation on serum adipsin, resistin and leptin. Twenty-two overweight or obese otherwise healthy adults were randomly assigned to receive either 2 g of carnosine ( = 13) or identically looking placebo ( = 9) for 12 weeks. Serum adipsin, leptin and resistin were analyzed using a bead-based multiplex assay. Carnosine supplementation decreased serum resistin concentrations compared to placebo (mean change from baseline: -35 ± 83 carnosine vs. 35 ± 55 ng/mL placebo, = 0.04). There was a trend for a reduction in serum leptin concentrations after carnosine supplementation (-76 ± 165 ng/mL carnosine vs. 20 ± 28 ng/mL placebo, = 0.06). The changes in leptin and resistin concentrations were inversely related to the change in concentration for urinary carnosine ( = -0.72, = 0.0002; = -0.67, = 0.0009, respectively), carnosine-propanal ( = -0.56, = 0.005; = -0.63, = 0.001, respectively) and carnosine-propanol ( = -0.61, = 0.002; = -0.60, = 0.002, respectively). There were no differences between groups in change in adipsin concentrations. Our findings show carnosine supplementation may normalize some, but not all, of the serum adipokine concentrations involved in glucose metabolism, in overweight and obese individuals. Further clinical trials with larger samples are needed to confirm these results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu10091258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165206PMC
September 2018

Carnosine supplementation reduces plasma soluble transferrin receptor in healthy overweight or obese individuals: a pilot randomised trial.

Amino Acids 2019 Jan 22;51(1):73-81. Epub 2018 Aug 22.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, Melbourne, VIC, 3168, Australia.

Abnormalities of iron homeostasis have been linked to insulin resistance, type 2 diabetes and cardiovascular disease. Carnosine, an over-the-counter food supplement with chelating properties, has been shown to decrease serum iron and improve glucose metabolism in diabetic rodents. We have previously demonstrated that carnosine supplementation prevented worsening of glucose metabolism in healthy overweight and obese middle-aged adults. Yet, the impact of carnosine on markers of iron metabolism in humans has not been investigated. We aimed to determine whether carnosine supplementation has an effect on iron parameters in overweight and obese, otherwise healthy adults. We included 26 participants, who were randomly allocated to receive 1 g carnosine (n = 14) or identical placebo (n = 12) twice daily for 12 weeks. Iron parameters including iron, ferritin, transferrin, soluble transferrin receptor, total iron binding capacity and iron saturation were measured in serum or plasma by standard commercial assays. Carnosine supplementation decreased plasma soluble transferrin receptor compared to placebo (mean change difference ± standard error: - 0.07 ± 0.03 mg/l, p = 0.04). None of the other iron parameters were different between carnosine and placebo groups. At follow-up, soluble transferrin receptor was associated inversely with urinary carnosine concentrations and positively with serum carnosinase-1 activity (both p < 0.02). Our findings suggest that carnosine may modulate iron metabolism in high-risk groups which could ameliorate insulin resistance and prevent type 2 diabetes. Larger human clinical trials are required to confirm our results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00726-018-2623-6DOI Listing
January 2019

Muscular Power during a Lifting Task Increases after Three Months of Resistance Training in Overweight and Obese Individuals.

Sports (Basel) 2017 Jun 8;5(2). Epub 2017 Jun 8.

Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava 83306, Slovakia.

Background: This study evaluates the effect on power produced during a modified lifting task in the overweight and obese after three months of either resistance or aerobic training.

Methods: Seventeen male subjects divided randomly into two groups performed deadlift and deadlift high pull, both with increasing weights up to maximal power, prior to and after the training programs (three sessions per week).

Results: Their mean power increased significantly during the deadlift at 20 kg (14.3%, p = 0.026), 30 kg (17.7%, p = 0.008), 40 kg (16.5%, p = 0.011), 50 kg (14.5%, p = 0.020), and 60 kg (14.3%, p = 0.021) and during the deadlift high pull at 30 kg (9.9%, p = 0.037), 40 kg (10.1%, p = 0.035), and 50 kg (8.2%, p = 0.044) after the resistance training. However, the group that participated in the aerobic training failed to show any significant changes in power performance during either the deadlift or deadlift high pull.

Conclusion: Three months of resistance training enhances power outputs during a lifting task with weights from 30 to 50 kg (~40%⁻60% of 1-repetition maximum) in the overweight and obese. Because this test was sensitive in revealing pre-post training changes in lifting performance, it should be implemented in the functional diagnostics for overweight and obese individuals and also complement existing testing methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/sports5020035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968996PMC
June 2017

Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients.

Endocr Regul 2018 Apr;52(2):110-118

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.

Objectives: Leigh syndrome is a progressive early onset neurodegenerative disease typically presenting with psychomotor regression, signs of brainstem and/or basal ganglia disease, lactic acidosis, and characteristic magnetic resonance imaging findings. At molecular level, deficiency of respiratory complexes and/or pyruvate dehydrogenase complex is usually observed. Nuclear gene SURF1 encodes an assembly factor for cytochrome c-oxidase complex of the respiratory chain and autosomal recessive mutations in SURF1 are one of the most frequent causes of cytochrome c-oxidase-related Leigh syndrome cases. Here, we aimed to elucidate the genetic basis of Leigh syndrome in three Slovak families.

Methods And Results: Three probands presenting with Leigh syndrome were selected for DNA analysis. The first proband, presenting with atypical LS onset without abnormal basal ganglia magnetic resonance imaging findings, was analyzed with whole exome sequencing. In the two remaining probands, SURF1 was screened by Sanger sequencing. Four different heterozygous mutations were identified in SURF1: c.312_321delinsAT:p.(Pro104Profs*1), c.588+1G>A, c.823_833+7del:p. (?) and c.845_846del:p.(Ser282Cysfs*9). All the mutations are predicted to have a loss-of-function effect.

Conclusions: We identified disease-causing mutations in all three probands, which points to the important role of SURF1 gene in etiology of Leigh syndrome in Slovakia. Our data showed that patients with atypical Leigh syndrome phenotype without lesions in basal ganglia may benefit from the whole exome sequencing method. In the case of probands presenting the typical phenotype, Sanger sequencing of the SURF1 gene seems to be an effective method of DNA analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2478/enr-2018-0013DOI Listing
April 2018

An acute bout of aerobic or strength exercise specifically modifies circulating exerkine levels and neurocognitive functions in elderly individuals with mild cognitive impairment.

Neuroimage Clin 2018 31;17:272-284. Epub 2017 Oct 31.

Division of Behavioral Neurology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan 704, Taiwan, ROC.; Alzheimer's Disease Research Center, National Cheng Kung University Hospital, Taiwan. Electronic address:

Although exercise is an effective way to decrease the risk of developing Alzheimer's disease, the biological basis for such benefits from the different exercise modes remains elusive. The present study thus aimed (i) to investigate the effects of acute aerobic or resistance exercise on neurocognitive performances and molecular markers when performing a cognitive task involving executive functioning in older adults with amnestic mild cognitive impairment (aMCI), and (ii) to explore relationships of acute exercise-induced neurocognitive changes with changes in circulating levels of neuroprotective growth factors (e.g., BDNF, IGF-1, VEGF, and FGF-2, collectively termed 'exerkines'), elicited by different acute exercise modes. Sixty-six older adults with aMCI were recruited and randomly assigned to an aerobic exercise (AE) group, a resistance exercise (RE) group, or a non-exercise-intervention (control) group. The behavioral [i.e., accuracy rate (AR) and reaction time (RT)] and electrophysiological [i.e., event-related potential (ERP) P3 latency and amplitude collected from the Fz, Cz, and Pz electrodes] indices were simultaneously measured when participants performed a Flanker task at baseline and after either an acute bout of 30 min of moderate-intensity AE, RE or a control period. Blood samples were taken at three time points, one at baseline (T1) and two after an acute exercise intervention (T2 and T3: before and after cognitive task test, respectively). The results showed that the acute AE and RE not only improved behavioral (i.e., RTs) performance but also increased the ERP P3 amplitudes in the older adults with aMCI. Serum FGF-2 levels did not change with acute aerobic or resistance exercise. However, an acute bout of aerobic exercise significantly increased serum levels of BDNF and IGF-1 and tended to increase serum levels of VEGF in elderly aMCI individuals. Acute resistance exercise increased only serum IGF-1 levels. However, the exercise-induced elevated levels of these molecular markers returned almost to baseline levels in T3 (about 20 min after acute exercise). In addition, changes in the levels of neurotrophic and angiogenic factors were not correlated with changes in RTs and P3 amplitudes. The present findings of changes in neuroprotective growth factors and neurocognitive performances through acute AE or RE suggest that molecular and neural prerequisites for exercise-dependent plasticity are preserved in elderly aMCI individuals. However, the distinct pattern of changes in circulating molecular biomarkers induced by two different exercise modes in aMCI elderly individuals and the potentially interactive mechanisms of the effects of BDNF, IGF-1, and VEGF on amyloid-β provide a basis for future long-term exercise intervention to investigate whether AE relative to RE might be more effective in prevention/treatment of an early stage neurodegenerative disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2017.10.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842646PMC
February 2019

Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte Inducibility through Glycerol Kinase.

Cell Rep 2018 01;22(3):760-773

Institute of Food, Nutrition and Health, ETH Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland. Electronic address:

Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPARα, β/δ, and γ, respectively. We found that both PPARα and β/δδ are dispensable for brown fat function. In contrast, we could show that ablation of PPARγ in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by β-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization. We identified glycerol kinase (Gyk) as a partial mediator of PPARγ function and could show that Gyk expression correlates with brown fat thermogenic capacity in human brown fat biopsies. Thus, Gyk might constitute the link between PPARγ-mediated regulation of brown fat function and activation by β-adrenergic signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2017.12.067DOI Listing
January 2018

Aerobic-Strength Exercise Improves Metabolism and Clinical State in Parkinson's Disease Patients.

Front Neurol 2017 22;8:698. Epub 2017 Dec 22.

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.

Regular exercise ameliorates motor symptoms in Parkinson's disease (PD). Here, we aimed to provide evidence that exercise brings additional benefits to the whole-body metabolism and skeletal muscle molecular and functional characteristics, which might help to explain exercise-induced improvements in the clinical state. 3-months supervised endurance/strength training was performed in early/mid-stage PD patients and age/gender-matched individuals ( = 11/11). The effects of exercise on resting energy expenditure (REE), glucose metabolism, adiposity, and muscle energy metabolism (P-MRS) were evaluated and compared to non-exercising PD patients. Two muscle biopsies were taken to determine intervention-induced changes in fiber type, mitochondrial content, and expression of genes related to muscle energy metabolism, as well as proliferative and regenerative capacity. Exercise improved the clinical disability score (MDS-UPDRS), bradykinesia, balance, walking speed, REE, and glucose metabolism and increased muscle expression of energy sensors (AMPK). However, the exercise-induced increase in muscle mass/strength, mitochondrial content, type II fiber size, and postexercise phosphocreatine (PCr) recovery (P-MRS) were found only in controls. Nevertheless, MDS-UPDRS was associated with muscle AMPK and mechano-growth factor (MGF) expression. Improvements in fasting glycemia were positively associated with muscle function and the expression of and , and the parameters of fitness/strength were positively associated with the expression of , and . Moreover, reduced bradykinesia was associated with better muscle metabolism (maximal oxidative capacity and postexercise PCr recovery; P-MRS). Exercise training improved the clinical state in early/mid-stage Parkinson's disease patients, including motor functions and whole-body metabolism. Although the adaptive response to exercise in PD was different from that of controls, exercise-induced improvements in the PD clinical state were associated with specific adaptive changes in muscle functional, metabolic, and molecular characteristics.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02253732.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2017.00698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743754PMC
December 2017

Effect of carnosine supplementation on the plasma lipidome in overweight and obese adults: a pilot randomised controlled trial.

Sci Rep 2017 12 12;7(1):17458. Epub 2017 Dec 12.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Carnosine has been shown to reduce oxidation and glycation of low density lipoprotein hence improving dyslipidaemia in rodents. The effect of carnosine on human plasma lipidome has thus far not been investigated. We aimed to determine whether carnosine supplementation improves the plasma lipidome in overweight and obese individuals. Lipid analysis was performed by liquid chromatography mass spectrometry in 24 overweight and obese adults: 13 were randomly assigned to 2 g carnosine daily and 11 to placebo, and treated for 12 weeks. Carnosine supplementation maintained trihexosylceramide (0.01 ± 0.19 vs -0.28 ± 0.34 nmol/ml, p = 0.04), phosphatidylcholine (77 ± 167 vs -81 ± 196 nmol/ml, p = 0.01) and free cholesterol (20 ± 80 vs -69 ± 80 nmol/ml, p = 0.006) levels compared to placebo. Trihexosylceramide was inversely related with fasting insulin (r = -0.6, p = 0.002), insulin resistance (r = -0.6, p = 0.003), insulin secretion (r = -0.4, p = 0.05) and serum carnosinase 1 activity (r = -0.3, p = 0.05). Both phosphatidylcholine and free cholesterol did not correlate with any cardiometabolic parameters. Our data suggest that carnosine may have beneficial effects on the plasma lipidome. Future larger clinical trials are needed to confirm this.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-17577-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727174PMC
December 2017

Genetic analysis of single-minded 1 gene in early-onset severely obese children and adolescents.

PLoS One 2017 4;12(5):e0177222. Epub 2017 May 4.

Laboratory of Diabetes and Metabolic Disorders, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.

Background: Inactivating mutations of the hypothalamic transcription factor singleminded1 (SIM1) have been shown as a cause of early-onset severe obesity. However, to date, the contribution of SIM1 mutations to the obesity phenotype has only been studied in a few populations. In this study, we screened the functional regions of SIM1 in severely obese children of Slovak and Moravian descent to determine if genetic variants within SIM1 may influence the development of obesity in these populations.

Methods: The SIM1 promoter region, exons and exon-intron boundaries were sequenced in 126 unrelated obese children and adolescents (2-18 years of age) and 41 adult lean controls of Slovak and Moravian origin. Inclusion criteria for the children and adolescents were a body mass index standard deviation score higher than 2 SD for an appropriate age and sex, and obesity onset at less than 5 years of age. The clinical phenotypes of the SIM1 variant carriers were compared with clinical phenotypes of 4 MC4R variant carriers and with 27 unrelated SIM1 and MC4R mutation negative obese controls that were matched for age and gender.

Results: Seven previously described SIM1 variants and one novel heterozygous variant p.D134N were identified. The novel variant was predicted to be pathogenic by 7 in silico software analyses and is located at a highly conserved position of the SIM1 protein. The p.D134N variant was found in an 18 year old female proband (BMI 44.2kg/m2; +7.5 SD), and in 3 obese family members. Regardless of early onset severe obesity, the proband and her brother (age 16 years) did not fulfill the criteria of metabolic syndrome. Moreover, the variant carriers had significantly lower preferences for high sugar (p = 0.02) and low fat, low carbohydrate, high protein (p = 0.02) foods compared to the obese controls.

Conclusions: We have identified a novel SIM1 variant, p.D134N, in 4 obese individuals from a single pedigree which is also associated with lower preference for certain foods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177222PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417716PMC
September 2017

EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO.

Hum Mutat 2017 04 23;38(4):409-425. Epub 2017 Jan 23.

Research Group Development and Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.

Impairment of translation initiation and its regulation within the integrated stress response (ISR) and related unfolded-protein response has been identified as a cause of several multisystemic syndromes. Here, we link MEHMO syndrome, whose genetic etiology was unknown, to this group of disorders. MEHMO is a rare X-linked syndrome characterized by profound intellectual disability, epilepsy, hypogonadism and hypogenitalism, microcephaly, and obesity. We have identified a C-terminal frameshift mutation (Ile465Serfs) in the EIF2S3 gene in three families with MEHMO syndrome and a novel maternally inherited missense EIF2S3 variant (c.324T>A; p.Ser108Arg) in another male patient with less severe clinical symptoms. The EIF2S3 gene encodes the γ subunit of eukaryotic translation initiation factor 2 (eIF2), crucial for initiation of protein synthesis and regulation of the ISR. Studies in patient fibroblasts confirm increased ISR activation due to the Ile465Serfs mutation and functional assays in yeast demonstrate that the Ile465Serfs mutation impairs eIF2γ function to a greater extent than tested missense mutations, consistent with the more severe clinical phenotype of the Ile465Serfs male mutation carriers. Thus, we propose that more severe EIF2S3 mutations cause the full MEHMO phenotype, while less deleterious mutations cause a milder form of the syndrome with only a subset of the symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267786PMC
April 2017

Three months of resistance training in overweight and obese individuals improves reactive balance control under unstable conditions.

J Back Musculoskelet Rehabil 2017 ;30(2):353-362

Slovak Academy of Sciences, Institute of Experimental Endocrinology, Bratislava, Slovakia.

Background: Contrary to static and dynamic balance, there is a lack of scientific evidence on the training induced changes in reactive balance control in response to unexpected perturbations in overweight and obese individuals.

Objective: This study evaluates the effect of 3 months of resistance and aerobic training programs on postural responses to unexpected perturbations under stable and unstable conditions in the overweight and obese.

Methods: A group of 17 overweight and obese subjects, divided into two groups, underwent either resistance or aerobic training for a period of 3 months (3 sessions per week). Prior to and after completing the training, they performed the load release balance test while standing on either a stable or unstable surface, with eyes open and closed.

Results: Peak posterior center of pressure (CoP) displacement, and the time to peak posterior CoP displacement during a bipedal stance on a foam surface with eyes open (17.3%, p = 0.019 and 15.4%, p = 0.029) and eyes closed (15.0%, p = 0.027 and 13.2%, p = 0.034), decreased significantly. In addition, the total anterior to posterior CoP displacement, and the time from peak anterior to peak posterior CoP displacement, both with eyes open (18.1%, p = 0.017 and 12.2%, p = 0.040) and eyes closed (16.3%, p = 0.023 and 11.7%, p = 0.044), also significantly decreased. However, after completing the resistance training, the parameters registered while standing on a stable platform, both with eyes open and closed, did not change significantly. The group that underwent an aerobic training also failed to show any significant changes in parameters of the load release balance test.

Conclusion: Three months of resistance training in overweight and obese subjects improves reactive balance control in response to unexpected perturbations under unstable conditions, both with and without visual cues. Due to the fact that this unstable load release balance test was found to be sensitive in revealing post-training changes, it would be suitable for implementing in the functional diagnostic for this group, in addition to complementing existing testing methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/BMR-160585DOI Listing
May 2017

Spatial variability and reproducibility of GABA-edited MEGA-LASER 3D-MRSI in the brain at 3 T.

NMR Biomed 2016 11 7;29(11):1656-1665. Epub 2016 Oct 7.

High Field MR Center, Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna, Austria.

The reproducibility of gamma-aminobutyric acid (GABA) quantification results, obtained with MRSI, was determined on a 3 T MR scanner in healthy adults. In this study, a spiral-encoded, GABA-edited, MEGA-LASER MRSI sequence with real-time motion-scanner-instability corrections was applied for robust 3D mapping of neurotransmitters in the brain. In particular, the GABA (i.e. GABA plus macromolecule contamination) and Glx (i.e. glutamate plus glutamine contamination) signal was measured. This sequence enables 3D-MRSI with about 3 cm nominal resolution in about 20 min. Since reliable quantification of GABA is challenging, the spatial distribution of the inter-subject and intra-subject variability of GABA and Glx levels was studied via test-retest assessment in 14 healthy volunteers (seven men-seven women). For both inter-subject and intra-subject repeated measurement sessions a low coefficient of variation (CV) and a high intraclass correlation coefficient (ICC) were found for GABA and Glx ratios across all evaluated voxels (intra-/inter-subject: GABA ratios, CV ~ 8%-ICC > 0.75; Glx ratios, CV ~ 6%-ICC > 0.70). The same was found in selected brain regions for Glx ratios versus GABA ratios (CV varied from about 5% versus about 8% in occipital and parietal regions, to about 8% versus about 10% in the frontal area, thalamus, and basal ganglia). These results provide evidence that 3D mapping of GABA and Glx using the described methodology provides high reproducibility for application in clinical and neuroscientific studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nbm.3613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095789PMC
November 2016

Unilateral Stability and Visual Feedback Body Control Improves After Three-Month Resistance Training in Overweight Individuals.

J Mot Behav 2017 Jul-Aug;49(4):398-406. Epub 2016 Oct 11.

b Institute of Experimental Endocrinology, Slovak Academy of Sciences , Bratislava , Slovakia.

The authors evaluated the effect of 3 months of resistance and aerobic training (3 sessions/week) on body balance in a group of 25 overweight and obese individuals. Prior to and after the training, they performed static and task-oriented balance tests under various conditions. Mean center of pressure (CoP) velocity and mean trace length of the CoP in the y-axis registered during a one-legged stance significantly decreased after the resistance training (19.1%, p = .024; 29.3%, p = .009). Mean trace length of the CoP in the y-axis decreased significantly also during a bipedal stance on a foam surface with eyes open and closed (10.9%, p = .040; 18.2%, p = .027). In addition, mean CoP distance and mean squared CoP distance in the anteroposterior direction during a visually guided center of mass (CoM) tracking task significantly improved (14.7%, p = .033; 28.2%, p = .016). However, only mean trace length of the CoP in the y-axis during a bipedal stance on a foam surface with eyes open and closed significantly decreased after the aerobic training (10.3%, p = .047; 16.5%, p = .029). It may be concluded that resistance training is more efficient for the improvement of the anteroposterior unilateral stability and the accuracy of the regulation of the CoM anteroposterior position than aerobic training in overweight and obese individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00222895.2016.1219307DOI Listing
September 2018