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1.
J Cell Biochem ; 124(4): 520-532, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36791261

RESUMO

Gluten intolerance is associated with several disorders in the body. Although research has grown in recent years, the understanding of its impact on different tissues and the effects of physical exercise in mitigating health problems in the condition of gluten intolerance are still limited. Therefore, our objective was to test whether gliadin would affect metabolism and inflammation in liver tissue and whether aerobic physical exercise would mitigate the negative impacts of gliadin administration in rodents. Wistar rats were divided into exercised gliadin, gliadin, and control groups. Gliadin was administered by gavage from birth to 60 days of age. The rats in the exercised gliadin group performed an aerobic running exercise training protocol for 15 days. At the end of the experiments, physiological, histological, and molecular analyzes were performed in the study. Compared to the control group, the gliadin group had impaired weight gain and increased gluconeogenesis, lipogenesis, and inflammatory biomarkers in the liver. On the other hand, compared to the gliadin group, animals in the exercise-gliadin group had a recovery in body weight, improved insulin sensitivity, and a reduction in some gluconeogenesis, lipogenesis, and inflammatory biomarkers in the liver. In conclusion, our results revealed that the administration of gliadin from birth impaired weight gain and induced an increase in hepatic inflammatory cytokines, which was associated with an impairment of glycemic homeostasis in the liver, all of which were attenuated by adding aerobic exercise training in the gliadin group.


Assuntos
Doença Celíaca , Gliadina , Ratos , Animais , Ratos Wistar , Doença Celíaca/metabolismo , Aumento de Peso , Inflamação/induzido quimicamente , Inflamação/terapia , Biomarcadores
2.
Cell Biochem Funct ; 41(1): 128-137, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36515301

RESUMO

Dysfunction of the adipose tissue metabolism is considered as a significant hallmark of aging. It has been proposed that α-ß hydrolase domain containing 5 (ABHD5) plays a critical role in the control of lipolysis. However, the role of ABHD5 in the control of lipolysis during aging or exercise is unknown. Here we combined the experimental mouse model with transcriptomic analyzes by using murine and human databases to explore the role of ABHD5 in the adipose tissue during aging and in response to exercise. Transcriptomic data revealed a downregulation of Abhd5 messenger RNA levels in the subcutaneous white adipose tissue (scWAT) over time in individuals from 20 to 69 years old. Aged mice displayed dramatic reduction of ABHD5 protein content and lipolytic-related proteins in the scWAT. Interestingly, 4 weeks of high-intensity interval training increased ABHD5 protein level and restored the lipolytic pathway in the scWAT of aged mice. Altogether, our findings demonstrated that aging affects ABHD5 content in the adipose tissue of mice and humans. Conversely, exercise increases ABHD5 activity, recovering the lipolytic activity in aged mice.


Assuntos
1-Acilglicerol-3-Fosfato O-Aciltransferase , Tecido Adiposo , Envelhecimento , Exercício Físico , Lipólise , Adulto , Idoso , Animais , Humanos , Camundongos , Pessoa de Meia-Idade , Adulto Jovem , 1-Acilglicerol-3-Fosfato O-Aciltransferase/genética , 1-Acilglicerol-3-Fosfato O-Aciltransferase/metabolismo , Tecido Adiposo/enzimologia , Envelhecimento/metabolismo , Hidrolases/genética , Hidrolases/metabolismo
3.
Life Sci ; 312: 121175, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36414092

RESUMO

Aging can modify the morphology and function of the liver, such as generating a decrease in the mitochondria content, autophagy, and cell senescence. Although exercise training has several beneficial effects on hepatic metabolism, its actions on autophagy processes, mitochondrial function, and cellular senescence need to be more widely explored. The present study verified the effects of aging and exercise on hepatic circadian markers, autophagy, and mitochondria activity in 24-month-old mice with a combined exercise training protocol. In addition, we used public datasets from human livers in several conditions and BMAL1 knockout mice. C57BL/6 mice were distributed into Control (CT, young, 6-month-old mice), sedentary old (Old Sed, sedentary, 24-month-old mice), and exercised old (Old Ex, 24-month-old mice submitted to a combined exercise training protocol). The exercise training protocol consisted of three days of endurance exercise - treadmill running, and two days of resistance exercise - climbing a ladder, for three weeks. At the end of the protocol, the liver was removed and prepared for histological analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunoblotting technique, and oxygen consumption. Heatmaps were built using a human dataset and Bmal1 knockout samples. In summary, the Old Sed had reduced strength, coordination, and balance, as well as a decrease in Bmal1 expression and the presence of degenerated liver cells. Still, this group upregulated the transcription factors related to mitochondrial biogenesis. The Old Ex group had increased strength, coordination, and balance, improved glucose sensitivity, as well as restored Bmal1 expression and the mitochondrial transcription factors. The human datasets indicated that mitochondrial markers and autophagy strongly correlate with specific liver diseases but not aging. We can speculate that mitochondrial and autophagy molecular markers alterations may depend on long-term training.


Assuntos
Fatores de Transcrição ARNTL , Fígado , Condicionamento Físico Animal , Animais , Camundongos , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo
4.
Front Immunol ; 13: 953272, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311768

RESUMO

Interleukin 6 (IL-6) acts as a pro and anti-inflammatory cytokine, has an intense correlation with exercise intensity, and activates various pathways such as autophagy and mitochondrial unfolded protein response. Also, IL-6 is interconnected to circadian clock-related inflammation and can be suppressed by the nuclear receptor subfamily 1, group D, member 1 (Nr1d1, protein product REV-ERBα). Since IL-6 is linked to physical exercise-modulated metabolic pathways such as autophagy and mitochondrial metabolism, we investigated the relationship of IL-6 with REV-ERBα in the adaptations of these molecular pathways in response to acute intense physical exercise in skeletal muscle. The present study was divided into three experiments. In the first one, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were divided into three groups: Basal time (Basal; sacrificed before the acute exercise), 1 hour (1hr post-Ex; sacrificed 1 hour after the acute exercise), and 3 hours (3hr post-Ex; sacrificed 3 hours after the acute exercise). In the second experiment, C2C12 cells received IL-6 physiological concentrations or REV-ERBα agonist, SR9009. In the last experiment, WT mice received SR9009 injections. After the protocols, the gastrocnemius muscle or the cells were collected for reverse transcription-quantitative polymerase chain reaction (RTq-PCR) and immunoblotting techniques. In summary, the downregulation of REV-ERBα, autophagic flux, and most mitochondrial genes was verified in the IL-6 KO mice independent of exercise. The WT and IL-6 KO treated with SR9009 showed an upregulation of autophagic genes. C2C12 cells receiving IL-6 did not modulate the Nr1d1 mRNA levels but upregulated the expression of some mitochondrial genes. However, when treated with SR9009, IL-6 and mitochondrial gene expression were upregulated in C2C12 cells. The autophagic flux in C2C12 suggest the participation of REV-ERBα protein in the IL-6-induced autophagy. In conclusion, the present study verified that the adaptations required through physical exercise (increases in mitochondrial content and improvement of autophagy machinery) might be intermediated by an interaction between IL-6 and REVERBα.


Assuntos
Interleucina-6 , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares , Animais , Camundongos , Autofagia/genética , Biomarcadores , Produtos do Gene rev , Interleucina-6/genética , Interleucina-6/metabolismo , Músculo Esquelético/metabolismo , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo
5.
Cell Biochem Funct ; 40(4): 369-378, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35411956

RESUMO

The intensity, duration, type of contraction, and muscle damage influence interleukin-6 (IL-6) response to acute exercise. However, in response to an exhaustive exercise session, the upregulation of IL-6 in the serum and heart is associated with an inflammatory condition and can inhibit autophagy. This study aimed to investigate the role of IL-6 in autophagy pathway responses and mitochondrial function in the heart of mice submitted to acute exhaustive physical exercise. The mice were allocated into three groups, five animals per group, for the wild type (WT) and the IL-6 knockout (IL-6 KO): Basal (sedentary; Basal), 1 h (after 1 h of the acute exercise; 1 h), and 3 h (after 3 h of the acute exercise; 3 h). After the specific time for each group, the blood was collected, each mouse heart was removed, and the left ventricle (LV) was isolated. In summary, under basal conditions, without the influence of the acute exercise, the IL-6 KO group showed lower number of nuclei in the cardiac tissue, but higher collagen deposition; lower messenger RNA (mRNA) levels of Prkaa1 and Mtco1, but higher mRNA levels of Ulk1; and higher protein levels of the ratio p-AMPK/AMPK in the heart when compared to WT at the same time point. After the acute exercise (1 and 3 h), the IL-6 KO group had lower mRNA levels of Tfam, Mtnd1, Mtco1, and Nampt in the heart when compared to WT after exercise; higher serum levels of creatine kinase (CK), CK-MB, and lactate dehydrogenase for the IL-6 group when compared to the WT group after the exercise. Specifically, the heat-shock protein 60 protein levels in the heart increased 3 h after exhaustive exercise in the WT group, but not in the IL-6 KO group. The study emphasizes that IL-6 may offer cardioprotective effects, including mitochondrial adaptations in response to acute exhaustive exercise.


Assuntos
Interleucina-6 , Condicionamento Físico Animal , Proteínas Quinases Ativadas por AMP , Animais , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Knockout , Condicionamento Físico Animal/fisiologia , RNA Mensageiro/metabolismo
6.
Nutrition ; 93: 111430, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34479044

RESUMO

OBJECTIVES: Based on taurine's beneficial roles in metabolic diseases in rodents and obese individuals, we investigated the effects of taurine supplementation on adipose tissue using transcriptome analysis, 3T3-L1 adipocytes, and subcutaneous white adipose tissue (scWAT) of obese women. METHODS: First, we applied bioinformatics analysis to evaluate the effect of the taurine synthesis pathway on the adipose tissue of several BXD mice strains. After that, using 3T3-L1 adipocytes, we investigated the effects of different taurine doses in proteins related to insulin signaling, lipid oxidation, and mitochondrial function. Finally, we evaluated the effects of taurine supplementation (3 grams, 8 wk) on the same proteins in the scWAT of obese women. RESULTS: The transcriptome analysis showed that the taurine biosynthesis pathway was positively associated with insulin signaling and mitochondrial metabolism in the scWAT of BXD mice. The experiments using 3T3-L1 cells highlighted that the taurine dosage has an essential function in taurine synthesis, insulin, and mitochondrial markers. In contrast, the 8-wk taurine administration did not change the basal insulin, proteins of the taurine synthesis or insulin pathways, lipid oxidation, or mitochondrial metabolism in the scWAT of obese women. CONCLUSIONS: For the first time, to our knowledge, we showed that supplementation with 3 g of taurine for 8 wk promoted no effect in the insulin signaling pathway in the scWAT of obese women. These findings bring new perspectives to investigate different taurine doses and the intervention period for human studies owing to the potential antiobesity activity of taurine.


Assuntos
Insulina , Taurina , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Insulina/metabolismo , Camundongos , Mitocôndrias , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Transdução de Sinais , Taurina/farmacologia
7.
Life Sci ; 285: 119988, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34592238

RESUMO

Strategies capable of attenuating TLR4 can attenuate metabolic processes such as inflammation, endoplasmic reticulum (ER) stress, and apoptosis in the body. Physical exercise has been a cornerstone in suppressing inflammation and dysmetabolic outcomes caused by TRL4 activation. Thus, the present study aimed to evaluate the effects of a chronic physical exercise protocol on the TLR4 expression and its repercussion in the inflammation, ER stress, and apoptosis pathways in mice hearts. Echocardiogram, RT-qPCR, immunoblotting, and histological techniques were used to evaluate the left ventricle of wild-type (WT) and Tlr4 knockout (TLR4 KO) mice submitted to a 4-week physical exercise protocol. Moreover, we performed a bioinformatics analysis to expand the relationship of Tlr4 mRNA in the heart with inflammation, ER stress, and apoptosis-related genes of several isogenic strains of BXD mice. The TLR4 KO mice had higher energy expenditure and heart rate in the control state but lower activation of apoptosis and ER stress pathways. The bioinformatics analysis reinforced these data. In the exercised state, the WT mice improved performance and cardiac function. However, these responses were blunted in the KO group. In conclusion, TLR4 has an essential role in the inhibition of apoptosis and ER stress pathways, as well as in the training-induced beneficial adaptations.


Assuntos
Apoptose/genética , Estresse do Retículo Endoplasmático/genética , Metabolismo Energético/genética , Ventrículos do Coração , Condicionamento Físico Animal , Receptor 4 Toll-Like/genética , Função Ventricular , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Ecocardiografia , Deleção de Genes , Glicogênio/metabolismo , Frequência Cardíaca , Inflamação/genética , Inflamação/patologia , Camundongos , Camundongos Knockout , RNA Mensageiro/metabolismo
8.
Front Immunol ; 12: 702025, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234788

RESUMO

Physical exercise is considered a fundamental strategy in improving insulin sensitivity and glucose uptake in skeletal muscle. However, the molecular mechanisms underlying this regulation, primarily on skeletal muscle glucose uptake, are not fully understood. Recent evidence has shown that Rho-kinase (ROCK) isoforms play a pivotal role in regulating skeletal muscle glucose uptake and systemic glucose homeostasis. The current study evaluated the effect of physical exercise on ROCK2 signaling in skeletal muscle of insulin-resistant obese animals. Physiological (ITT) and molecular analysis (immunoblotting, and RT-qPCR) were performed. The contents of RhoA and ROCK2 protein were decreased in skeletal muscle of obese mice compared to control mice but were restored to normal levels in response to physical exercise. The exercised animals also showed higher phosphorylation of insulin receptor substrate 1 (IRS1 Serine 632/635) and protein kinase B (Akt) in the skeletal muscle. However, phosphatase and tensin homolog (PTEN) and protein-tyrosine phosphatase-1B (PTP-1B), both inhibitory regulators for insulin action, were increased in obesity but decreased after exercise. The impact of ROCK2 action on muscle insulin signaling is further underscored by the fact that impaired IRS1 and Akt phosphorylation caused by palmitate in C2C12 myotubes was entirely restored by ROCK2 overexpression. These results suggest that the exercise-induced upregulation of RhoA-ROCK2 signaling in skeletal muscle is associated with increased systemic insulin sensitivity in obese mice and further implicate that muscle ROCK2 could be a potential target for treating obesity-linked metabolic disorders.


Assuntos
Resistência à Insulina/fisiologia , Insulina/metabolismo , Camundongos Obesos/metabolismo , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Quinases Associadas a rho/metabolismo , Animais , Glucose/metabolismo , Camundongos , Camundongos Obesos/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiopatologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Transdução de Sinais/fisiologia
9.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807902

RESUMO

Although physical exercise-induced autophagy activation has been considered a therapeutic target to enhance tissue health and extend lifespan, the effects of different exercise models on autophagy in specific metabolic tissues are not completely understood. This descriptive investigation compared the acute effects of endurance (END), exhaustive (ET), strength (ST), and concurrent (CC) physical exercise protocols on markers of autophagy, genes, and proteins in the gastrocnemius muscle, heart, and liver of mice. The animals were euthanized immediately (0 h) and six hours (6 h) after the acute exercise for the measurement of glycogen levels, mRNA expression of Prkaa1, Ppargc1a, Mtor, Ulk1, Becn1, Atg5, Map1lc3b, Sqstm1, and protein levels of Beclin 1 and ATG5. The markers of autophagy were measured by quantifying the protein levels of LC3II and Sqstm1/p62 in response to three consecutive days of intraperitoneal injections of colchicine. In summary, for gastrocnemius muscle samples, the main alterations in mRNA expressions were observed after 6 h and for the ST group, and the markers of autophagy for the CC group were increased (i.e., LC3II and Sqstm1/p62). In the heart, the Beclin 1 and ATG5 levels were downregulated for the ET group. Regarding the markers of autophagy, the Sqstm1/p62 in the heart tissue was upregulated for the END and ST groups, highlighting the beneficial effects of these exercise models. The liver protein levels of ATG5 were downregulated for the ET group. After the colchicine treatment, the liver protein levels of Sqstm1/p62 were decreased for the END and ET groups compared to the CT, ST, and CC groups. These results could be related to diabetes and obesity development or liver dysfunction improvement, demanding further investigations.


Assuntos
Autofagia , Regulação da Expressão Gênica , Proteínas Musculares/biossíntese , Músculo Esquelético/metabolismo , Condicionamento Físico Animal , Animais , Biomarcadores/metabolismo , Masculino , Camundongos
10.
Am J Physiol Endocrinol Metab ; 320(3): E488-E495, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33459179

RESUMO

Brown adipose tissue (BAT) has been encouraged as a potential treatment for obesity and comorbidities due to its thermogenic activity capacity and contribution to energy expenditure. Some interventions such as cold and ß-adrenergic drugs are able to activate BAT thermogenesis as well as promote differentiation of white adipocytes into brown-like cells (browning), enhancing the thermogenic activity of these cells. In this mini-review, we discuss new mechanisms related to BAT and energy expenditure. In this regard, we will also discuss recent studies that have revealed the existence of important secretory molecules from BAT "batokines" that act in autocrine, paracrine, and endocrine mechanisms, which in turn may explain some of the beneficial roles of BAT on whole body glucose and fat metabolism. Finally, we will discuss new insights related to BAT thermogenesis with an additional focus on the distinct features of BAT metabolism between rodents and humans.


Assuntos
Tecido Adiposo Marrom/fisiologia , Adipócitos Brancos/metabolismo , Animais , Metabolismo Energético/fisiologia , Glucose/metabolismo , Humanos , Termogênese/fisiologia
11.
J Anat ; 238(3): 743-750, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33094520

RESUMO

The anatomy of the hypothalamus includes many nuclei and a complex network of neurocircuits. In this context, some hypothalamic nuclei reside closer to the blood-brain barrier, allowing communication with the peripheral organs through some molecules, such as leptin. Leptin is considered the main adipokine for energy homeostasis control. Furthermore, leptin signalling in the hypothalamus can communicate with insulin signalling through the activation of phosphoinositide 3-kinase (PI3k). Previous data suggest that isoforms of PI3k are necessary to mediate insulin action in the hypothalamus. However, obese animals show impairment in the central signalling of these hormones. Thus, in the current study, we evaluated the role of acute exercise in the leptin and insulin pathways in the hypothalamus, as well as in food intake control in obese mice. Although acute physical exercise was not able to modulate leptin signalling, this protocol suppressed the increase in the suppressor of cytokine signalling 3 (SOCS3) protein levels. In addition, acute exercise increased the content of PI3k-p110α protein in the hypothalamus. The exercised animals showed a strong tendency to reduction in cumulative food intake. For the first time, our results indicate physical exercise can increase PI3k-p110α protein content in the hypothalamus of obese mice and regulate food intake.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Hipotálamo/metabolismo , Leptina/metabolismo , Obesidade/terapia , Condicionamento Físico Animal/fisiologia , Animais , Masculino , Camundongos , Obesidade/metabolismo
12.
Eur J Nutr ; 59(6): 2427-2437, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31494696

RESUMO

PURPOSE: Nicotinamide riboside (NR) acts as a potent NAD+ precursor and improves mitochondrial oxidative capacity and mitochondrial biogenesis in several organisms. However, the effects of NR supplementation on aerobic performance remain unclear. Here, we evaluated the effects of NR supplementation on the muscle metabolism and aerobic capacity of sedentary and trained mice. METHODS: Male C57BL/6 J mice were supplemented with NR (400 mg/Kg/day) over 5 and 10 weeks. The training protocol consisted of 5 weeks of treadmill aerobic exercise, for 60 min a day, 5 days a week. Bioinformatic and physiological assays were combined with biochemical and molecular assays to evaluate the experimental groups. RESULTS: NR supplementation by itself did not change the aerobic performance, even though 5 weeks of NR supplementation increased NAD+ levels in the skeletal muscle. However, combining NR supplementation and aerobic training increased the aerobic performance compared to the trained group. This was accompanied by an increased protein content of NMNAT3, the rate-limiting enzyme for NAD + biosynthesis and mitochondrial proteins, including MTCO1 and ATP5a. Interestingly, the transcriptomic analysis using a large panel of isogenic strains of BXD mice confirmed that the Nmnat3 gene in the skeletal muscle is correlated with several mitochondrial markers and with different phenotypes related to physical exercise. Finally, NR supplementation during aerobic training markedly increased the amount of type I fibers in the skeletal muscle. CONCLUSION: Taken together, our results indicate that NR may be an interesting strategy to improve mitochondrial metabolism and aerobic capacity.


Assuntos
Aerobiose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NAD/metabolismo , Niacinamida/análogos & derivados , Compostos de Piridínio/metabolismo , Compostos de Piridínio/farmacologia , Animais , Respiração Celular/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Niacinamida/metabolismo , Niacinamida/farmacologia
13.
Life Sci ; 240: 117107, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785241

RESUMO

BACKGROUND: Toll-like receptor 4 (Tlr4) is recognized due to its role in the immune response. Also, this protein can participate in the signaling pathway of events triggered by physical exercise such as apoptosis, inflammation, and endoplasmic reticulum (ER) stress. The main objective of this study was to evaluate the role of Tlr4 in the markers of these events in the myocardium of mice submitted to acute physical exercise (APE) protocols at different intensities. METHODS: Echocardiogram, RT-qPCR, and immunoblotting technique were used to evaluate the left ventricle of wild-type (WT) and Tlr4 knockout (Tlr4 KO) submitted to APE protocols at 45, 60, and 75% of their maximal velocity. Also, we performed the bioinformatics analysis to establish the connection of heart mRNA levels of Tlr4 with heart genes of inflammation and ER stress of several isogenic strains of BXD mice. RESULTS: Under basal conditions, the Tlr4 deletion diminished the performance, and expression of inflammation and ER stress genes in the left ventricle, but increased the serum levels of CK, Il-17, and Tnf-alpha. Under the same exercise conditions, the Tlr4 deletion reduced the glycemia, serum levels of CK, Il-17, and Tnf-alpha, as well as genes and/or proteins related to apoptosis, inflammation and ER stress in the left ventricle, but increased the levels of CK-mb and LDH, as well as other genes related to apoptosis, inflammation, and ER stress in the left ventricle. CONCLUSION: Altogether, the current findings highlighted the effects of different acute exercise intensities were attenuated in the heart of Tlr4 KO mice.


Assuntos
Apoptose/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Coração/fisiologia , Inflamação , Esforço Físico/fisiologia , Receptor 4 Toll-Like/fisiologia , Animais , Apoptose/genética , Biologia Computacional , Creatina Quinase/sangue , Ecocardiografia , Estresse do Retículo Endoplasmático/genética , Coração/diagnóstico por imagem , Interleucina-17/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Esforço Físico/genética , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/sangue
14.
J Cell Physiol ; 234(1): 880-890, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-30078194

RESUMO

This study investigated the effects of exercise training in regulating inflammatory processes, endoplasmic reticulum stress, and apoptosis in hypothalamic neurons of obese mice. Swiss mice were distributed into three groups: Lean mice (Lean), sedentary animals fed a standard diet; obese mice (Obese), sedentary animals fed a high-fat diet (HFD); trained obese mice (T. Obese), animals fed with HFD and concurrently subjected to an endurance training protocol for 8 weeks. In the endurance training protocol, mice ran on a treadmill at 60% of peak workload for 1 hr, 5 days/week for 8 weeks. Twenty-four hours after the last exercise session, the euthanasia was performed. Western blot, quantitative real-time polymerase chain reaction, and terminal deoxynucleotide transferase biotin-dUTP nick end-labeling (TUNEL) techniques were used for the analysis of interest. The results show exercise training increased phosphorylation of leptin signaling pathway proteins (pJAK2/pSTAT3) and reduced the content of tumor necrosis factor α, toll-like receptor 4, suppressor of cytokine signaling 3, protein-tyrosine phosphatase 1B as well as the phosphorylation of IkB kinase in the hypothalamus of T. Obese animals. A reduction of macrophage activation and phosphorylation of eukaryotic initiation factor 2α, and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were also observed in exercised animals. Furthermore, exercise decreased the expression of the proapoptotic protein (PARP1) and increased anti-inflammatory (IL-10) and antiapoptotic (Bcl2) proteins. Using the TUNEL technique, we observed that the exercised animals had lower DNA fragmentation. Finally, physical exercise preserved pro-opiomelanocortin messenger RNA content. In conclusion, exercise training was able to reorganize the control of the energy balance through anti-inflammatory and antiapoptotic responses in hypothalamic tissue of obese mice.


Assuntos
Treino Aeróbico , Inflamação/fisiopatologia , Obesidade/terapia , Condicionamento Físico Animal , Animais , Apoptose/genética , Dieta Hiperlipídica , Metabolismo Energético/genética , Regulação da Expressão Gênica , Humanos , Hipotálamo/metabolismo , Hipotálamo/patologia , Inflamação/terapia , Interleucina-10/genética , Camundongos , Camundongos Obesos , Neurônios/metabolismo , Neurônios/patologia , Obesidade/fisiopatologia , Poli(ADP-Ribose) Polimerase-1/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética
15.
J Cell Biochem ; 119(7): 5885-5892, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29575149

RESUMO

The accumulation of fatty acids in the liver associated with obesity condition is also known as nonalcoholic fatty liver disease (NAFLD). The impaired fat oxidation in obesity condition leads to increased hepatic fat accumulation and increased metabolic syndrome risk. On the other hand, physical exercise has been demonstrated as a potent strategy in the prevention of NAFLD. Also, these beneficial effects of exercise occur through different mechanisms. Recently, the Cdc2-like kinase (CLK2) protein was associated with the suppression of fatty acid oxidation and hepatic ketogenesis. Thus, obese animals demonstrated elevated levels of hepatic CLK2 and decreased fat acid oxidation. Here, we explored the effects of chronic physical exercise in the hepatic metabolism of obese mice. Swiss mice were distributed in Lean, Obese (fed with high-fat diet during 16 weeks) and Trained Obese group (fed with high-fat diet during 16 weeks and exercised (at 60% exhaustion velocity during 1 h/5 days/week) during 8 weeks. In our results, the obese animals showed insulin resistance, increased hepatic CLK2 content and increased hepatic fat accumulation compared to the Lean group. Otherwise, the chronic physical exercise improved insulin resistance state, prevented the increased CLK2 in the liver and attenuated hepatic fat accumulation. In summary, these data reveal a new protein involved in the prevention of hepatic fat accumulation after chronic physical exercise. More studies can evidence the negative role of CLK2 in the control of liver metabolism, contributing to the improvement of insulin resistance, obesity, and type 2 diabetes.


Assuntos
Resistência à Insulina , Lipogênese , Fígado/enzimologia , Obesidade/terapia , Condicionamento Físico Animal , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Magreza/fisiopatologia , Animais , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/enzimologia , Obesidade/etiologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética
16.
Life Sci ; 194: 98-103, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29273527

RESUMO

AIMS: Sestrins, a class of stress-related proteins, is involved in the control of aging-induced organic dysfunctions and metabolic control. However, the factors that modulate the levels of Sestrins are poorly studied. Here, we evaluated the effects of acute and chronic aerobic exercise on Sestrin 1 (Sesn1) and Sesn2 protein contents in the skeletal muscle of mice. MAIN METHODS: Male C57BL/6J mice performed an acute or chronic (4weeks) exercise protocols on a treadmill running at 60% of the peak workload. Then, the quadriceps muscle was removed and analyzed by Western blot. Bioinformatics analysis was also performed to evaluate Sesn1 and Sesn2 mRNA in the skeletal muscle and phenotypic pattern in a large panel of isogenic strains of BXD mice. KEY FINDINGS: While acute aerobic exercise increased Sesn1 accumulation and induced a discrete augment of Sesn2 protein content and AMPK threonine phosphorylation, chronic exercise reduced the basal levels of Sesn1 and Sesn2 as well as of AMPK threonine phosphorylation in the quadriceps muscles of C57BL/6J mice. In accordance with these experimental approaches, transcriptomic analysis revealed that Sesn1 and Sesn2 mRNA levels in the skeletal muscle were inversely correlated with the locomotor activity in several strains of BXD mice. SIGNIFICANCE: Our data suggest that physical exercise has role on Sestrin1 and Sestrin2 expression on skeletal muscle, providing new insights into the mechanism by which physical exercise affects stress-related proteins in skeletal muscles.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Músculo Esquelético/fisiologia , Proteínas Nucleares/metabolismo , Proteínas Quinases Ativadas por AMP/análise , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Proteínas de Ciclo Celular/análise , Masculino , Camundongos Endogâmicos C57BL , Proteínas Nucleares/análise , Peroxidases , Fosforilação , Condicionamento Físico Animal , Corrida
17.
J Cell Physiol ; 233(6): 4791-4800, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29219181

RESUMO

The effects of physical exercise on insulin signaling and glycemic homeostasis are not yet fully understood. Recent findings elucidated the positive role of Rho-kinase (Rock) in increasing the glucose uptake through insulin receptor substrate-1 (IRS1) phosphorylation in the skeletal muscle. Here, we explored the effects of short-term exercise on Rock activity and insulin signaling. Fischer 344 rats (3 months old) were subjected to a short-term swimming exercise for 2 hr per day for 5 days, with an overload corresponding to 1.5% of body weight. As expected, the exercised group had a reduced glycemia and increased insulin sensitivity. The contents of Rock1, Rock2, and Rock activity were improved in the skeletal muscle of the exercised rats. The contents of RhoA and RhoGEF, which are proteins involved in the Rock metabolism, were also increased in the skeletal muscle after exercise. These changes in the protein contents were accompanied by an increase in the insulin signaling pathway (pIRS1/pPDK/pAkt/pGSK3ß/pAS160/GLUT4), Rock activity, and IRS1 phosphorylation at the 632/635 serine residues. On the other hand, when Rock was inhibited with the Y-27632, the insulin sensitivity in response to exercise was impaired. Based on these findings, we conclude that the short-term exercise increased both insulin sensitivity and glucose tolerance, through the increased Rock activity and pIRS1 (serine 632/635) mediated by Rock, in the skeletal muscle of Fischer 344 rats. These data represent an exercise-mediated novel mechanism, suggesting an essential role of Rock activity in the insulin signaling and glucose homeostasis improvement.


Assuntos
Insulina/metabolismo , Contração Muscular , Músculo Esquelético/enzimologia , Condicionamento Físico Animal , Esforço Físico , Quinases Associadas a rho/metabolismo , Animais , Glicemia/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Masculino , Fosforilação , Ratos Endogâmicos F344 , Transdução de Sinais , Natação , Fatores de Tempo
18.
Front Cell Neurosci ; 11: 313, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29062272

RESUMO

Mitogen-activated Protein Kinase Phosphatase 3 (MKP-3) has been involved in the negative regulation of insulin signaling. The absence of MKP-3 is also associated with reduced adiposity, increased energy expenditure and improved insulin sensitivity. The MKP-3 is known as the main Erk1/2 phosphatase and FoxO1 activator, which has repercussions on the gluconeogenesis pathway and hyperglycemia in obese mice. Recently, we showed that MKP-3 overexpression decreases FoxO1 phosphorylation in the hypothalamus of lean mice. However, the hypothalamic interaction between MKP-3 and FoxO1 during obesity was not investigated yet. Here, the MKP-3 expression and the effects on food intake and energy expenditure, were investigated in high-fat diet-induced obese mice. The results indicate that obesity in mice increased the MKP-3 protein content in the hypothalamus. This hypothalamic upregulation led to an increase of food intake, adiposity, and body weight. Furthermore, the obese mice with increased MKP-3 showed an insulin signaling impairment with reduction of insulin-induced FoxO1 and Erk1/2 phosphorylation in the hypothalamus. Moreover, a bioinformatics analysis of data demonstrated that hypothalamic MKP-3 mRNA levels were positively correlated with body weight and negatively correlated to oxygen consumption (VO2) in BXD mice. Taken together, our study reports that obesity is associated with increased protein levels of hypothalamic MKP-3, which is related to the reduction of FoxO1 and Erk1/2 phosphorylation in the hypothalamus as well as to an increase in body weight and a reduction in energy expenditure.

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