Jozef Ukropec

• PhD
• Principal Investigator at Slovak Academy of Sciences

Background: Trends in global ageing underscore the rising burden of age-related cognitive decline and concomitant cardiometabolic diseases, including type 2 diabetes mellitus (T2DM). Carnosine, a naturally occurring dipeptide with anti-inflammatory, antioxidant and anti-glycating properties, has shown promise in animal models and limited human stud...

Background Low levels of vitamin D have been associated with several autoimmune diseases. A growing body of evidence supports the association of vitamin D with skeletal muscle damage, regeneration, and energy and lipid metabolism. The aim was to analyse vitamin D and its receptor (VDR) in the muscle tissue of patients with idiopathic inflammatory m...

Background The risk of cognitive decline in cancer survivors may be increased by platinum‐based chemotherapy. Evidence indicates that physical exercise has a potential to reduce chemotherapy‐related toxicity. The aim of this study was to assess effects of a 6‐month aerobic‐strength training on cognitive functions, metabolic flexibility, anthropomet...

Background Physical exercise improves clinical state of patients with Parkinson’s disease (PD), and evidence from experimental models suggests it has a potential to slow down the disease progression. Improved glucose metabolism as well as exerkines, bioactive molecules released into circulation with each exercise bout, contribute to the synchronize...

Background Platinum‐based chemotherapy provides curative treatment to more than 95% of patients with testicular germ cell tumor but it has negative cardiometabolic and neurological effects. Regular exercise can alleviate late chemotherapy‐related toxicities. We examined the impact of a 6‐month supervised aerobic‐strength training on cognitive and c...

Objectives Objective of this work was to examine myomiR levels in plasma, skeletal muscle, and skeletal muscle cells of patients with idiopathic inflammatory myopathy (IIM), their interrelations with the disease-related clinical phenotypes and with the effects of the disease-modifying 6-month training-intervention. Methods Samples of vastus latera...

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associa...

Acetylcarnitine is an essential metabolite for maintaining metabolic flexibility and glucose homeostasis. The in vivo behavior of muscle acetylcarnitine content during exercise has not been shown with magnetic resonance spectroscopy. Therefore, this study aimed to explore the behavior of skeletal muscle acetylcarnitine during rest, plantar flexion...

The present study aimed to investigate the acute effects of aerobic exercise with different intensities on executive-related oculomotor control and cerebral dopamine/serotonin/norepinephrine metabolite concentrations in individuals with Parkinson’s disease (PD). Twenty-eight PD individuals completed acute bouts of high-intensity interval exercise (...

Background Exercise improves physical fitness, cognitive functions & metabolism in the elderly. Evidence from animal models suggests the role for mediators from muscle or adipose tissue in the exercise‐induced brain plasticity (1). Knowledge on the regulation of these potentially neuroprotective molecules by exercise in humans is limited (2,3). We...

Background Thyroid hormones play an important role in energy metabolism and weight control, explained mostly by inducing thermogenesis and increasing basal metabolic rate. It has recently been shown that FT4 levels are associated with food preferences, which might also play a role in modulating body weight. The aim of this longitudinal follow-up st...

Purposes Physical activity (PA) may mitigate late cardiometabolic toxicity of cisplatin-based chemotherapy in testicular germ cell tumor (TGCT) long-term survivors. In this cross-sectional study, we evaluated the effects of habitual PA on metabolic syndrome (MetS) prevalence, and on the markers of cardiometabolic health and chronic inflammation in...

Objective Strong evidence supports the benefits of exercise for healthy ageing, including reduced risk of neurodegenerative diseases. Recent studies suggested interorgan crosstalk as a key element of systemic adaptive response, however, the role of specific molecules in mediating exercise effects on the human brain are not fully understood. In the...

Context Type 2 diabetes mellitus (T2D) negatively affects muscle mass and function throughout life. Whether adult muscle stem cells contribute to the decrease in muscle health is not clear and insights into the stem cell niche are difficult to obtain. Objective To establish the upstream signalling pathway of microRNA (miR)-501, a marker of activat...

Carnosine is a performance-enhancing food supplement with a potential to modulate muscle energy metabolism and toxic metabolites disposal. In this study we explored interrelations between carnosine supplementation (2g/day, 12 weeks) induced effects on carnosine muscle loading and parallel changes in (i) muscle energy metabolism, (ii) serum albumin...

Backround: Extracellular vesicles (EVs) are released into circulation during exercise and can transfer cargo to recipient tissues, thus contributing to the systemic exercise-induced adaptive response. Methods: EVs were isolated from serum & cerebrospinal fluid/CSF (n=5/6) of young healthy active adults (26.0y±4.0yrs, BMI xz±xz kg/m 2; VO2max 50.1±1...

Background Thyroid hormones profoundly affect energy metabolism but their interrelation with food preference, which might contribute to childhood obesity development, are much less understood. In this study, we investigated if thyroid hormone levels are associated with specific modulation of food preference and potentially linked to the level of ob...

Metabolomics has emerged as a powerful new tool in precision medicine. No studies have yet been published on the metabolomic changes in cerebrospinal fluid (CSF) produced by acute endurance exercise. CSF and plasma were collected from 19 young active adults (13 males and 6 females) before and 60 min after a 90‐min monitored outdoor run. The median...

Background Idiopathic inflammatory myopathies (IIM) are chronic inflammatory disorders characterised, apart from extramuscular manifestations, by symmetrical progressive muscle weakness that may persist even after pharmacological suppression of inflammation, suggesting a significant involvement of nonimmune mechanisms. Low levels of vitamin D have...

Background Persistent muscle weakness after reduction of inflammation and resistance to immunosuppressive therapy in some patients with idiopathic inflammatory myopathies (IIM) suggest that not only immune but also non-immune mechanisms, such as mitochondrial abnormalities and metabolic disturbance, contribute to the pathogenesis of myositis. Exerc...

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) tr...

Objectives: Idiopathic inflammatory myopathies/IIM are associated with changes in muscle-specific microRNA/miR. Exercise improves muscle function and metabolism in parallel with changes in miR expression. We investigated the effects of disease and exercise on miRs in differentiated muscle cells/myotubes from IIM patients and controls. Methods: S...

Activation of thermogenic brown and beige adipocytes is considered as a strategy to improve metabolic control. Here, we identify GPR180 as a receptor regulating brown and beige adipocyte function and whole-body glucose homeostasis, whose expression in humans is associated with improved metabolic control. We demonstrate that GPR180 is not a GPCR but...

A wealth of evidence has shown that a single bout of aerobic exercise can facilitate executive function. However, none of current studies on this topic have addressed whether the magnitude of the acute-exercise benefit on executive function and oculomotor performance is influenced by different aerobic exercise modes. The present study was thus aime...

Aim Afamin is a liver-produced glycoprotein, a potential early marker of metabolic syndrome. Here we investigated regulation of afamin in a course of the metabolic disease development and in response to 3-month exercise intervention. Methods We measured whole-body insulin sensitivity (euglycemic hyperinsulinemic clamp), glucose tolerance, abdomina...

Cold exposure results in activation of metabolic processes required for fueling thermogenesis, potentially promoting improved metabolic health. However, the metabolic complexity underlying this process is not completely understood. We aimed to analyze changes in plasma metabolites related to acute cold exposure and their relationship to cold-acclim...

Testicular germ cell tumors (TGCTs) represent ∼95% of testicular malignancies and are the most common type of malignancy in young male adults. While the incidence of TGCTs has increased during the last decades, the advances in treatment, namely introducing cisplatin into the chemotherapy regimen, have made TGCTs highly curable with the 10-year surv...

Introduction: A new role for parathyroid hormone (PTH) in adipose tissue metabolic activation and browning, including cancer cachexia-related wasting, has been described recently. Regulation of these processes via PTH receptor (PTH1R) may be important in the maintenance of wholebody metabolic homeostasis in both obesity and cachexia. Here, we measu...

Background Physical inactivity accelerates ageing‐associated cognitive decline while regular physical exercise improves neurocognitive health, in parallel with improvements of physical fitness and whole‐body metabolism. However, the knowledge on putative bioactive molecules, mediators of exercise benefits in human brain is still very limited. Our a...

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...

Key points Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM). In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6‐month intensive supervised training intervention to assess the impact of disease and...

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...

Adipose tissue is usually classified on the basis of its function as white, brown or beige (brite)1. 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 complications2,3. In addition, adipose tissue functions as a signalling hub that regulat...

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 (rs1...

Purpose: Aging is associated with changes in muscle energy metabolism. Proton (¹H) and phosphorous (³¹P) 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 ³...

Background Idiopathic inflammatory myopathies (IIM, myositis) are a heterogeneous group of autoimmune muscle disorders characterized by skeletal muscle weakness and damage, inflammation and extramuscular manifestations. Recent findings suggest that immunological as well as nonimmunological processes, such as endoplasmic reticulum stress, hypoxia, m...

Background It has been demonstrated several times that endurance exercise has beneficial effects on the condition of patients with idiopathic inflammatory myopathies (IIM). Muscle contraction during exercise is a major stimulus for the release of myokines that are supposed to take part in the beneficial adaption to exercise. Objectives The aim of...

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 15min ice-water swimming (IWS, n=15) or 120-150min of co...

Introduction: The objective of the study was to examine the relationship between the values of selected parameters of physical function, body composition, body mass index (BMI) and biochemical markers of metabolic health with the total testosterone (TT) levels in adult males. We aimed to analyse the correlation between these values and variations...

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 perf...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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 patien...

Adipose tissue usually is classified as either white, brown or beige/brite, based on whether it functions as an energy storage or thermogenic organ. It serves as an important regulator of systemic metabolism, exemplified by the fact that dysfunctional adipose tissue in obesity leads to a host of secondary metabolic complications such as diabetes, c...

Context: Cold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood. Objective: To investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans. Design: Cross-sectional study examining acute response to ice-water swimming and to ex...

Objasnenie mechanizmov regulácie metabolickej rovnováhy môže mať vzhľadom na stúpajúcu prevalenciu obezity a metabolických ochorení veľký klinický význam. Biele tukové tkanivo je svojimi anatomickými, morfologickými a metabolickými vlastnosťami prispôsobené na dlhodobé uskladňovanie veľkého množstva energie vo forme kva-pôčok neutrálnych lipidov. B...

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 intervent...

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...

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...

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 t...

Exercise can prevent the sedentary lifestyle-related risk of metabolic and cognitive decline, but mechanisms and mediators of exercise effects on human brain are relatively unexplored. We measured acute exercise-induced changes in adiponectin, insulin and other bioactive molecules in cerebrospinal fluid (CSF) and serum from young lean individuals....

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 preve...

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 (...

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...

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 combin...

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...

Abnormalities of iron homeostasis has been shown to cause insulin resistance, type 2 diabetes and cardiovascular disease. Treatment with iron chelators has shown to reverse several chronic diseases including type 2 diabetes. Carnosine, an over-the-counter food supplement with chelating properties, has been shown to lower serum iron and glucose conc...

Adipokines play an important role in the regulation of glucose metabolism. We have previously shown that carnosine supplementation in overweight or obese nondiabetic individuals improved glucose metabolism but did not change adiponectin levels, however its effect on other adipokines has not been investigated. We aimed to determine the effect of car...

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...

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...

Continuous exposure to cold leads to activation of adaptive thermogenesis in brown adipose tissue but also to induction of brown/beige cell phenotype in white adipose tissue. The aim of this work was to investigate whether prior exposure to immobilization (IMO) stress may affect immune response associated with adipocyte “browning” in mesenteric adi...

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...

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...

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...

This study evaluates the effect of 3 months resistance and aerobic training on muscle strength and power in 17 male overweight and obese men. Subjects underwent either a resistance or aerobic training for a period of 3 months (three sessions per week). Peak isometric force, rate of force development, peak power and height of countermovement and squ...

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 performi...

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...

Biele tukové tkanivo je orgán, ktorý dokáže v adipocytoch akumulovať obrovské množstvo energie a v závislosti od stavu naplnenia energetických zásob produkovať celé spektrum bioaktívnych látok (adipokínov). Týmito mediátormi reguluje napríklad príjem potravy alebo metabolickú aktivitu tkanív s cieľom zabezpečiť asi všetky energeticky náročné biolog...

Purpose This study evaluates the effect of 3 month resistance and aerobic training programs on step initiation speed and foot tapping frequency in the overweight and obese. Methods Twenty-five overweight and obese subjects were divided into two groups and participated in either resistance or aerobic training for a period of 3 months (3 sessions per...

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...

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 obes...

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 multi-systemic 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...

Supporting information

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 p...

While Bmp4 has a well-established role in the commitment of mesenchymal stem cells into the adipogenic lineage, its role in brown adipocyte formation and activity is not well defined. Here, we show that Bmp4 has a dual function in adipogenesis by inducing adipocyte commitment while inhibiting the acquisition of a brown phenotype during terminal dif...

Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacen...

Catecholamines (CAs) are mainly produced by sympathoadrenal system but their de novo production has been also observed in adipose tissue cells. The aim of this work was to investigate whether immune challenge induced by lipopolysaccharide (LPS) modulates biosynthesis of CAs in mesenteric adipose tissue (MWAT), as well as whether previous exposure t...

Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and meta...