RESUMO
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.
Assuntos
Carnosina/administração & dosagem , Quelantes/administração & dosagem , Suplementos Nutricionais , Ferro/sangue , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Receptores da Transferrina/sangue , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Carnosina/farmacologia , Quelantes/farmacologia , Feminino , Ferritinas/sangue , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Sobrepeso/sangue , Projetos Piloto , Transferrina/metabolismoRESUMO
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.
Assuntos
Epilepsia , Fator de Iniciação 2 em Eucariotos/genética , Hipogonadismo , Deficiência Intelectual/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Microcefalia , Mutação , Sequência de Aminoácidos , Saúde da Família , Feminino , Genitália/anormalidades , Humanos , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/patologia , Obesidade , Linhagem , Análise de Sequência de DNA/métodos , Homologia de Sequência de Aminoácidos , SíndromeRESUMO
Irisin was identified as a myokine secreted by contracting skeletal muscle, possibly mediating some exercise health benefits via 'browning' of white adipose tissue. However, a controversy exists concerning irisin origin, regulation and function in humans. Thus, we have explored Fndc5 gene and irisin protein in two clinical studies: (i) a cross-sectional study (effects of type 2 diabetes (T2D) in drug-naive men) and (ii) an intervention study (exercise effects in sedentary, overweight/obese individuals). Glucose tolerance and insulin sensitivity were assessed. Maximal aerobic capacity and muscle strength were measured before and after training. Body composition (magnetic resonance imaging), muscle and liver fat content (1H-magnetic resonance spectroscopy (MRS)) and in vivo muscle metabolism (32P-MRS) were determined. Skeletal muscle and subcutaneous abdominal adipose tissue samples were taken in the fasted state and during euglycaemic hyperinsulinaemia (adipose tissue) and before/after exercise training (muscle). We found that muscle Fndc5 mRNA was increased in prediabetes but not T2D. Fndc5 in adipose tissue and irisin in plasma were reduced in T2D by 40% and 50%, respectively. In contrast, T2D-derived myotubes expressed/secreted the highest levels of Fndc5/irisin. Neither hyperinsulinaemia (adipose tissue/plasma) nor exercise (muscle/plasma) affected Fndc5/irisin in vivo. Circulating irisin was positively associated with muscle mass, strength and metabolism and negatively with fasting glycaemia. Glucose and palmitate decreased Fndc5 mRNA in myotubes in vitro. We conclude that distinct patterns of Fndc5/irisin in muscle, adipose tissue and circulation, and concordant in vivo down-regulation in T2D, indicate that irisin might distinguish metabolic health and disease. Moreover, Fndc5/irisin was discordantly regulated in diabetic muscle and myotubes in vitro, suggesting that whole body factors, such as glucose and fatty acids, might be important for irisin regulation. Exercise did not affect Fndc5/irisin. However, irisin was positively linked to muscle mass, strength and metabolism, pointing to common regulatory factors and/or the potential for irisin to modify muscle phenotype.
Assuntos
Tecido Adiposo/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Terapia por Exercício , Fibronectinas/metabolismo , Músculo Esquelético/fisiopatologia , Obesidade/fisiopatologia , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/reabilitação , Feminino , Humanos , Masculino , Obesidade/complicações , Obesidade/reabilitaçãoRESUMO
Catecholamines (CATs), the major regulator of lipolysis in adipose tissue, are produced mainly by the sympathoadrenal system. However, recent studies report endogenous CAT production in adipocytes themselves. This study investigated the effects of single and repeated (7-14 times) immobilization (IMO) stress on CAT production in various fat depots of the rat. Single IMO quickly induced a rise of norepinephrine (NE) and epinephrine (EPI) concentration in mesenteric and brown adipose depots. Adaptive response to repeated IMO included robust increases of NE and EPI levels in mesenteric and subcutaneous adipose tissue. These changes likely reflect the activation of sympathetic nervous system in fat depots by IMO. However, this process was also paralleled by an increase in tyrosine hydroxylase gene expression in mesenteric fat, suggesting regulation of endogenous CAT production in adipose tissue cells. Detailed time-course analysis (time course 10, 30, and 120 min) clearly showed that repeated stress led to increased CAT biosynthesis in isolated mesenteric adipocytes resulting in gradual accumulation of intracellular EPI during IMO exposure. Comparable changes were also found in stromal/vascular fractions, with more pronounced effects of single than repeated IMO. The potential physiological importance of these findings is accentuated by parallel increase in expression of vesicular monoamine transporter 1, indicating a need for CAT storage in adipocyte vesicles. Taken together, we show that CAT production occurs in adipose tissue and may be activated by stress directly in adipocytes.
Assuntos
Adipócitos/metabolismo , Tecido Adiposo Branco/metabolismo , Catecolaminas/metabolismo , Restrição Física/psicologia , Estresse Psicológico/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/irrigação sanguínea , Tecido Adiposo Branco/inervação , Animais , Epinefrina/metabolismo , Regulação Enzimológica da Expressão Gênica , Masculino , Mesentério , Norepinefrina/metabolismo , Feniletanolamina N-Metiltransferase/genética , Feniletanolamina N-Metiltransferase/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/etiologia , Células Estromais/metabolismo , Gordura Subcutânea/metabolismo , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Regulação para Cima , Proteínas Vesiculares de Transporte de Monoamina/genética , Proteínas Vesiculares de Transporte de Monoamina/metabolismoRESUMO
BACKGROUND: CD40, a transmembrane receptor of the tumor necrosis factor gene superfamily, is activated in response to cellular stress, including hypoxia, and orchestrates the process of inflammation via secondary messengers such as mitogen-activated protein kinase kinase 4 (MKK4) and c-Jun NH(2)-terminal kinases (JNK). OBJECTIVES: We hypothesized that CD40, MKK4 and JNK expression is increased in the adipose tissue of patients with very severe chronic obstructive pulmonary disease (COPD). METHODS: In 20 patients with stable COPD, lung function was assessed using body plethysmography, and samples of subcutaneous adipose tissue were analyzed using real-time PCR. Body composition, including fat mass index (FMI), was assessed by bioelectrical impedance. RESULTS: 12 patients in GOLD stage I-III (age 61.6 ± 8.6 years, 4 females, mean partial pressure of oxygen in arterial blood, PaO(2), 9.38 ± 0.21 kPa) were compared to 8 patients in GOLD stage IV (age 62.6 ± 6.3 years, all male, mean PaO(2) 7.70 ± 0.37 kPa). Compared to patients in GOLD stage I-III, patients in GOLD stage IV had lower FMI (p = 0.004), being associated with significantly higher adipose tissue expression of CD40, MKK4 and JNK [ΔΔCt: 2.55 (1.99, 4.40) vs. 1.87 (1.63, 2.23), p = 0.013; 5.19 (3.13, 5.96) vs. 2.98 (2.82, 3.86), p = 0.002; 9.01 (5.12, 11.41) vs. 4.65 (4.42, 6.26), p = 0.001, respectively]. Log-transformed CD40, MKK4 and JNK expression was significantly inversely related to PaO(2), respectively. CONCLUSIONS: Upregulation of proinflammatory CD40, MKK4 and JNK gene expression in adipose tissue in very severe COPD raises the possibility of a role of chronic systemic hypoxia in the pathogenesis of adipose tissue inflammation in COPD.
Assuntos
Tecido Adiposo/metabolismo , Antígenos CD40/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , MAP Quinase Quinase 4/metabolismo , Adipócitos/patologia , Composição Corporal , Feminino , Expressão Gênica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica , Regulação para Cima/fisiologiaRESUMO
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-acclimatization level and metabolic health in cold-acclimatized humans. Blood samples were obtained before and acutely after 10-15 min of ice-water swimming (<5 °C) from 14 ice-water swimmers. Using mass spectrometry, 973 plasma metabolites were measured. Ice-water swimming induced acute changes in 70 metabolites. Pathways related to amino acid metabolism were the most cold-affected and cold-induced changes in several amino acids correlated with cold-acclimatization level and/or metabolic health markers, including atherogenic lipid profile or insulin resistance. Metabolites correlating with cold-acclimatization level were enriched in the linoleic/α-linolenic acid metabolic pathway. N-lactoyl-tryptophan correlated with both cold-acclimatization level and cold-induced changes in thyroid and parathyroid hormones. Acute cold stress in cold-acclimatized humans induces changes in plasma metabolome that involve amino acids metabolism, while the linoleic and α-linolenic acid metabolism pathway seems to be affected by regular cold exposure. Metabolites related to metabolic health, thermogenic hormonal regulators and acclimatization level might represent prospective molecular factors important in metabolic adaptations to regular cold exposure.
RESUMO
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, abdominal adiposity, hepatic lipid content (magnetic resonance imaging/spectroscopy), habitual physical activity (accelerometers) and serum afamin (enzyme-linked immunosorbent assay) in 71 middle-aged men with obesity, prediabetes and newly diagnosed type 2 diabetes. Effects of 3-month exercise were investigated in 22 overweight-to-obese middle-aged individuals (16M/6F). Results: Prediabetes and type 2 diabetes, but not obesity, were associated with increased serum afamin (p<0.001). Afamin correlated positively with hepatic lipids, fatty liver index and liver damage markers; with parameters of adiposity (waist circumference, %body fat, adipocyte diameter) and insulin resistance (fasting insulin, C-peptide, HOMA-IR; p<0.001 all). Moreover, afamin negatively correlated with whole-body insulin sensitivity (M-value/Insulin, p<0.001). Hepatic lipids and fasting insulinemia were the most important predictors of serum afamin, explaining >63% of its variability. Exercise-related changes in afamin were paralleled by reciprocal changes in insulinemia, insulin resistance and visceral adiposity. No significant change in hepatic lipid content was observed. Conclusions: Subjects with prediabetes and type 2 diabetes had the highest serum afamin levels. Afamin was more tightly related to hepatic lipid accumulation, liver damage and insulin resistance than to obesity.
Assuntos
Adiposidade , Biomarcadores/sangue , Proteínas de Transporte/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Fígado Gorduroso/diagnóstico , Glicoproteínas/sangue , Obesidade/fisiopatologia , Estado Pré-Diabético/diagnóstico , Adulto , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Fígado Gorduroso/sangue , Feminino , Seguimentos , Humanos , Resistência à Insulina , Metabolismo dos Lipídeos , Masculino , Estado Pré-Diabético/sangue , Prognóstico , Albumina Sérica HumanaRESUMO
Potential links between metabolic derangements and adipose tissue (AT) inflammation in patients with chronic obstructive pulmonary disease (COPD) are unexplored. We investigated AT expressions of interleukin (IL)-6, tumor necrosis factor (TNF)-α, CD68 (macrophage cell surface receptor), caspase-3, and Bax, and their relationships to the metabolic phenotype in nine cachectic, 12 normal-weight, 12 overweight, and 11 obese patients with COPD (age 62.3 ± 7.2 years). With increasing body mass index, increases in AT expressions of IL-6, TNF-α, and CD68 were observed (P < .001; P = .005; P < .001, resp.), in association with reduced insulin sensitivity (P < .001). No differences were observed between cachectic and normal-weight patients in AT expressions of inflammatory or proapoptotic markers. Adipose tissue CD68 and TNF-α expressions predicted insulin sensitivity independently of known confounders (P = .005; P = .025; R(2) = 0.840). Our results suggest that AT inflammation in obese COPD patients relates to insulin resistance. Cachectic patients remain insulin sensitive, with no AT upregulation of inflammatory or proapoptotic markers.
Assuntos
Tecido Adiposo/patologia , Mediadores da Inflamação/metabolismo , Inflamação/patologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Idoso , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Caquexia/complicações , Caquexia/genética , Caquexia/metabolismo , Caquexia/patologia , Caspase 3/genética , Feminino , Expressão Gênica , Humanos , Resistência à Insulina/fisiologia , Interleucina-6/genética , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Sobrepeso/complicações , Sobrepeso/genética , Sobrepeso/metabolismo , Sobrepeso/patologia , Paniculite/complicações , Paniculite/genética , Paniculite/metabolismo , Paniculite/patologia , Fenótipo , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa/genética , Proteína X Associada a bcl-2/genéticaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
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 (nâ =â 15) or 120 to 150 minutes of cold-induced nonshivering thermogenesis (NST) applied to cold-acclimatized (nâ =â 6) or non-acclimatized (nâ =â 11) individuals. Deep-neck brown adipose tissue (BAT) was collected from non-acclimatized patients undergoing elective neck surgery (nâ =â 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.
Assuntos
Aclimatação/fisiologia , Tecido Adiposo Marrom/metabolismo , Temperatura Baixa , Hormônio Paratireóideo/sangue , Hormônios Tireóideos/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Insulina/sangue , Iodeto Peroxidase/metabolismo , Masculino , Pessoa de Meia-Idade , Pescoço , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Natação , Tireotropina/sangue , Proteína Desacopladora 1/metabolismo , Iodotironina Desiodinase Tipo IIRESUMO
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.
Assuntos
Doença de Leigh/genética , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Doença de Leigh/diagnóstico por imagem , Doença de Leigh/patologia , Doença de Leigh/fisiopatologia , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas Mitocondriais/antagonistas & inibidores , Mutação , Linhagem , Eslováquia , Sequenciamento do ExomaRESUMO
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 (n = 13) or identically looking placebo (n = 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, p = 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, p = 0.06). The changes in leptin and resistin concentrations were inversely related to the change in concentration for urinary carnosine (r = -0.72, p = 0.0002; r = -0.67, p = 0.0009, respectively), carnosine-propanal (r = -0.56, p = 0.005; r = -0.63, p = 0.001, respectively) and carnosine-propanol (r = -0.61, p = 0.002; r = -0.60, p = 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.
Assuntos
Carnosina/administração & dosagem , Suplementos Nutricionais , Obesidade/terapia , Resistina/sangue , Adulto , Biomarcadores/sangue , Método Duplo-Cego , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Projetos Piloto , Eslováquia , Resultado do TratamentoRESUMO
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 squat jumps, reactive strength index, and mean power in the concentric phase of bench presses were all assessed prior to and after completing the training program. Results identified a significant increase of mean power during both countermovement bench presses at 30 kg (18.6%, p = .021), 40 kg (14.6%, p = .033), and 50 kg (13.1%, p = .042) and concentric-only bench presses at 30 kg (19.6%, p = .017) and 40 kg (13.9%, p = .037) after the resistance training. There was also a significant increase in the height of the jump (12.8%, p = .013), peak power (10.1%, p = .026), and peak velocity (9.7%, p = .037) during the countermovement jump and height of the jump (11.8%, p = .019), peak power (9.6%, p = .032), and peak velocity (9.5%, p = .040) during the squat jump. There were no significant changes in the reactive strength index, peak force, and the rate of force development after the resistance training. The aerobic group failed to show any significant improvements in these parameters. It may be concluded that 3 months of resistance training without caloric restriction enhances upper and lower body muscle power in overweight and obese men.
Assuntos
Força Muscular , Obesidade , Treinamento Resistido , Adulto , Teste de Esforço/métodos , Humanos , Masculino , Aptidão Física/fisiologiaRESUMO
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.
Assuntos
Retroalimentação Sensorial/fisiologia , Sobrepeso/reabilitação , Equilíbrio Postural/fisiologia , Treinamento Resistido/métodos , Adulto , Humanos , Masculino , Obesidade/reabilitação , Resultado do TratamentoRESUMO
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.
Assuntos
Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Equilíbrio Postural/fisiologia , Postura/fisiologia , Treinamento Resistido/métodos , Adulto , Humanos , MasculinoRESUMO
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.
Assuntos
Carnosina/uso terapêutico , Suplementos Nutricionais , Lipídeos/sangue , Sobrepeso/sangue , Sobrepeso/terapia , Adulto , Biomarcadores/sangue , Método Duplo-Cego , Dislipidemias/sangue , Dislipidemias/terapia , Feminino , Humanos , Masculino , Projetos Piloto , Resultado do TratamentoRESUMO
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%â»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.
RESUMO
OBJECTIVE: Carnosine is a naturally present dipeptide in humans and an over-the counter food additive. Evidence from animal studies supports the role for carnosine in the prevention and treatment of diabetes and cardiovascular disease, yet there is limited human data. This study investigated whether carnosine supplementation in individuals with overweight or obesity improves diabetes and cardiovascular risk factors. METHODS: In a double-blind randomized pilot trial in nondiabetic individuals with overweight and obesity (age 43 ± 8 years; body mass index 31 ± 4 kg/m(2) ), 15 individuals were randomly assigned to 2 g carnosine daily and 15 individuals to placebo for 12 weeks. Insulin sensitivity and secretion, glucose tolerance (oral glucose tolerance test), blood pressure, plasma lipid profile, skeletal muscle ((1) H-MRS), and urinary carnosine levels were measured. RESULTS: Carnosine concentrations increased in urine after supplementation (P < 0.05). An increase in fasting insulin and insulin resistance was hampered in individuals receiving carnosine compared to placebo, and this remained significant after adjustment for age, sex, and change in body weight (P = 0.02, P = 0.04, respectively). Two-hour glucose and insulin were both lower after carnosine supplementation compared to placebo in individuals with impaired glucose tolerance (P < 0.05). CONCLUSIONS: These pilot intervention data suggest that carnosine supplementation may be an effective strategy for prevention of type 2 diabetes.
Assuntos
Carnosina/administração & dosagem , Glucose/metabolismo , Adulto , Glicemia/análise , Peso Corporal , Diabetes Mellitus Tipo 2/sangue , Suplementos Nutricionais , Método Duplo-Cego , Jejum , Feminino , Intolerância à Glucose , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Sobrepeso/sangue , Projetos Piloto , Placebos , Fatores de RiscoRESUMO
Growth hormone (GH) supplementation therapy to adults with GH deficiency has beneficial effects on adipose tissue lipid metabolism, improving thus adipocyte functional morphology and insulin sensitivity. However, molecular nature of these effects remains unclear. We therefore tested the hypothesis that lipid-mobilizing adipokine zinc-α2-glycoprotein is causally linked to GH effects on adipose tissue lipid metabolism. Seventeen patients with severe GH deficiency examined before and after the 5-year GH replacement therapy were compared with age-, gender- and BMI-matched healthy controls. Euglycemic hyperinsulinemic clamp was used to assess whole-body and adipose tissue-specific insulin sensitivity. Glucose tolerance was determined by oGTT, visceral and subcutaneous abdominal adiposity by MRI, adipocyte size morphometrically after collagenase digestion, lipid accumulation and release was studied in differentiated human primary adipocytes in association with GH treatment and zinc-α2-glycoprotein gene silencing. Five-year GH replacement therapy improved glucose tolerance, adipose tissue insulin sensitivity and reduced adipocyte size without affecting adiposity and whole-body insulin sensitivity. Adipose tissue zinc-α2-glycoprotein expression was positively associated with whole-body and adipose tissue insulin sensitivity and negatively with adipocyte size. GH treatment to adipocytes in vitro increased zinc-α2-glycoprotein expression (>50%) and was paralleled by enhanced lipolysis and decreased triglyceride accumulation (>35%). Moreover, GH treatment improved antilipolytic action of insulin in cultured adipocytes. Most importantly, silencing zinc-α2-glycoprotein eliminated all of the GH effects on adipocyte lipid metabolism. Effects of 5-year GH supplementation therapy on adipose tissue lipid metabolism and insulin sensitivity are associated with zinc-α2-glycoprotein. Presence of this adipokine is required for the GH action on adipocyte lipid metabolism in vitro.
RESUMO
BACKGROUND: Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists. METHODS AND RESULTS: Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography), % body fat (bioimpedance), abdominal subcutaneous and visceral adiposity (magnetic resonance imaging), insulin sensitivity (euglycaemic hyperinsulinemic clamp), resting energy expenditure (REE, indirect calorimetry), free-living ambulatory physical activity (accelerometers) and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years) with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04) and subcutaneous (r = 0.38, p = 0.02) but not visceral fat (r = 0.17, p = 0.33). Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008), REE (r = -0.58, p<0.001) and HDL-cholesterol levels (r = -0.34, p = 0.048). Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity. CONCLUSION: Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.