Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 119
Filtrar
1.
J Med Food ; 27(8): 749-757, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39017636

RESUMO

The study aimed to evaluate the effects of Pereskia aculeata Miller (ora-pro-nobis [OPN]) flour on body and biochemical parameters, thermogenic activity, and molecular expression of markers in the muscle tissue of mice subjected to resistance training (RT). Twelve mice were randomly assigned to two groups (n=6 animals/group): G1: control (Control) fed a standard diet + RT and G2: experimental (OPN) fed a diet based on OPN flour + RT. The RT consisted of a 6-week program using a vertical ladder combined with a fixed weight attached to the animal. Several parameters were measured, including assessment of body composition, biochemical markers, thermogenic activity, and molecular (mRNA expression of interleukin (IL)-6, fibronectin type III domain-containing protein 5 (FNDC5), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The OPN group exhibited a decrease in body weight and visceral adiposity, higher energy expenditure, and lipid oxidation rate. In addition, it was observed an increase in muscle volume and in mRNA expression levels of IL-6, FNDC5, PGC-1α, and TFAM. These findings suggest that OPN flour could be a nutritional option to enhance performance in RT.


Assuntos
Farinha , Interleucina-6 , Músculo Esquelético , Miocinas , Treinamento Resistido , Animais , Humanos , Masculino , Camundongos , Composição Corporal/efeitos dos fármacos , Metabolismo Energético , Fibronectinas/metabolismo , Fibronectinas/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Músculo Esquelético/metabolismo , Miocinas/genética , Miocinas/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Condicionamento Físico Animal , Termogênese/efeitos dos fármacos
2.
J Photochem Photobiol B ; 258: 112991, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39033547

RESUMO

INTRODUCTION: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Ischemic heart disease is one of the most harmful conditions to cellular structure and function. After reperfusion treatment, a spectrum of adverse effects becomes evident, encompassing altered cell viability, heightened oxidative stress, activated autophagy, and increased apoptosis. Photobiomodulation (PBM) has been utilized in experimental models of cardiac hypoxia to enhance mitochondrial response and ameliorate biochemical changes in injured tissue. However, the effects of PBM on cultured cardiomyocytes subjected to hypoxia/reoxygenation are not yet well established. METHOD: H9C2 cardiomyocytes were exposed to hypoxia with concentrations of 300 µM CoCl2 for 24 h, followed by 16 h of reoxygenation through incubation in a normoxic medium. Treatment was conducted using GaAIAs Laser (850 nm) after hypoxia at an intensity of 1 J/cm2. Cells were divided into three groups: Group CT (cells maintained under normoxic conditions), Group HR (cells maintained in hypoxia and reoxygenation conditions without treatment), Group HR + PBM (cells maintained in hypoxia and reoxygenation conditions that underwent PBM treatment). Cell viability was analyzed using MTT, and protein expression was assessed by western blot. One-way ANOVA with the Tukey post hoc test was used for data analysis. Differences were significant when p < 0.05. RESULTS: PBM at an intensity of 1 J/cm2 mitigated the alterations in cell survival caused by hypoxia/reoxygenation. Additionally, it significantly increased the expression of proteins Nrf2, HSP70, mTOR, LC3II, LC3II/I, and Caspase-9, while reducing the expression of PGC-1α, SOD2, xanthine oxidase, Beclin-1, LC3I, and Bax. CONCLUSION: PBM at intensities of 1 J/cm2 reverses the changes related to oxidative stress, mitochondrial biogenesis, autophagy, and apoptosis caused by hypoxia and reoxygenation in a culture of cardiomyocytes.


Assuntos
Apoptose , Autofagia , Hipóxia Celular , Sobrevivência Celular , Miócitos Cardíacos , Estresse Oxidativo , Miócitos Cardíacos/efeitos da radiação , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Sobrevivência Celular/efeitos da radiação , Animais , Ratos , Linhagem Celular , Hipóxia Celular/efeitos da radiação , Autofagia/efeitos da radiação , Estresse Oxidativo/efeitos da radiação , Apoptose/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Oxigênio/metabolismo , Cobalto/química , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo
3.
Shock ; 62(3): 410-415, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38888558

RESUMO

ABSTRACT: Mitochondrial dysfunction is a recognized feature of sepsis, characterized by ultrastructural damage, diminished oxidative phosphorylation, and depletion of mitochondrial antioxidant capacity observed in deceased septic patients. LPS tolerance induces a controlled response to sepsis. This study aimed to evaluate the function of tolerant mitochondria after cecal ligation and puncture (CLP)-induced sepsis. Mytochondrial oxygen consumption was determined using polarography. Extraction and quantification of RNA for the expression of Tfam, Nrf-1, and Ppargc-1α, and respiratory complex activity were measured. CLP-tolerant animals presented preserved respiratory rates of S3 and S4 and a ratio of respiratory control (RCR) compared to CLP-nontolerant animals with reduced oxidative phosphorylation and increased uncoupled respiration. Complex I Vmax was reduced in septic animals; however, CLP animals sustained normal Vmax. Mitochondrial biogenesis was preserved in CLP-tolerant animals compared to the CLP-nontolerant group, likely due to increased TFAM expression. LPS tolerance protected septic animals from mitochondrial dysfunction, favoring mitochondrial biogenesis and preserving mitochondrial respiration and respiratory complex I activity.


Assuntos
Lipopolissacarídeos , Mitocôndrias , Choque Séptico , Animais , Lipopolissacarídeos/farmacologia , Masculino , Mitocôndrias/metabolismo , Ratos , Choque Séptico/metabolismo , Biogênese de Organelas , Consumo de Oxigênio , Ratos Wistar , Fatores de Transcrição/metabolismo , Proteínas Mitocondriais/metabolismo , Respiração Celular/efeitos dos fármacos , Respiração Celular/fisiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos
4.
Gene ; 926: 148606, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38788813

RESUMO

Obesity and overweight are multifactorial diseases affecting more than one-third of the world's population. Physical inactivity contributes to a positive energy balance and the onset of obesity. Exercise combined with a balanced diet is an effective non-pharmacological strategy to improve obesity-related disorders. Gallic acid (GA), is a natural endogenous polyphenol found in a variety of fruits, vegetables, and wines, with beneficial effects on energetic homeostasis. The present study aims to investigate the effects of exercise training on obese mice supplemented with GA. Animal experimentation was performed with male Swiss mice divided into five groups: ST (standard control), HFD (obese control), HFD + GA (GA supplement), HFD + Trained (training), and HFD + GA + Trained (GA and training). The groups are treated for eight weeks with 200 mg/kg/body weight of the feed compound and, if applicable, physical training. The main findings of the present study show that GA supplementation improves liver fat, body weight, adiposity, and plasma insulin levels. In addition, animals treated with the GA and a physical training program demonstrate reduced levels of anxiety. Gene expression analyses show that Sesn2 is activated via PGC-1α independent of the GATOR2 protein, which is activated by GA in the context of physical activity. These data are corroborated by molecular docking analysis, demonstrating the interaction of GA with GATOR2. The present study contributes to understanding the metabolic effects of GA and physical training and demonstrates a new hepatic mechanism of action via Sestrin 2 and PGC-1α.


Assuntos
Ácido Gálico , Fígado , Camundongos Obesos , Obesidade , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Condicionamento Físico Animal , Animais , Camundongos , Ácido Gálico/farmacologia , Masculino , Fígado/metabolismo , Fígado/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/genética , Obesidade/tratamento farmacológico , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Ansiedade/tratamento farmacológico , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Sestrinas
5.
Braz J Med Biol Res ; 57: e13235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511769

RESUMO

The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1ß, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.


Assuntos
Lesão Pulmonar Aguda , Sepse , Camundongos , Animais , Pioglitazona , Regulação para Cima , PPAR gama/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Sepse/complicações , Lipopolissacarídeos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
6.
Int J Mol Sci ; 24(24)2023 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-38139395

RESUMO

During the antiretroviral era, individuals living with HIV continue to experience milder forms of HIV-associated neurocognitive disorder (HAND). Viral proteins, including Tat, play a pivotal role in the observed alterations within the central nervous system (CNS), with mitochondrial dysfunction emerging as a prominent hallmark. As a result, our objective was to examine the expression of genes associated with mitophagy and mitochondrial biogenesis in the brain exposed to the HIV-1 Tat protein. We achieved this by performing bilateral stereotaxic injections of 100 ng of HIV-1 Tat into the hippocampus of Sprague-Dawley rats, followed by immunoneuromagnetic cell isolation. Subsequently, we assessed the gene expression of Ppargc1a, Pink1, and Sirt1-3 in neurons using RT-qPCR. Additionally, to understand the role of Tert in telomeric dysfunction, we quantified the activity and expression of Tert. Our results revealed that only Ppargc1a, Pink1, and mitochondrial Sirt3 were downregulated in response to the presence of HIV-1 Tat in hippocampal neurons. Interestingly, we observed a reduction in the activity of Tert in the experimental group, while mRNA levels remained relatively stable. These findings support the compelling evidence of dysregulation in both mitophagy and mitochondrial biogenesis in neurons exposed to HIV-1 Tat, which in turn induces telomeric dysfunction.


Assuntos
Infecções por HIV , HIV-1 , Transtornos Neurocognitivos , Sirtuína 3 , Produtos do Gene tat do Vírus da Imunodeficiência Humana , Animais , Ratos , Produtos do Gene tat/metabolismo , Infecções por HIV/metabolismo , HIV-1/metabolismo , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/virologia , Neurônios/metabolismo , Biogênese de Organelas , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Sirtuína 3/genética , Sirtuína 3/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
7.
Biochem Pharmacol ; 217: 115852, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37832793

RESUMO

We studied the effect of cotadutide, a dual agonist glucagon-like peptide 1 (GLP1)/Glucagon, on interscapular brown adipose tissue (iBAT) remodeling and thermogenesis of obese mice. Twelve-week-old male C57BL/6 mice were fed a control diet (C group, n = 20) or a high-fat diet (HF group, n = 20) for ten weeks. Then, animals were redivided, adding cotadutide treatment: C, CC, HF, and HFC for four additional weeks. The multilocular brown adipocyte structure showed fat conversion (whitening), hypertrophy, and structural disarray in the HF group, which was reverted in cotadutide-treated animals. Cotadutide enhances the body temperature, thermogenesis, and sympathetic innervation (peroxisome proliferator-activated receptor-α, ß3 adrenergic receptor, interleukin 6, and uncoupled protein 1), reduces pro-inflammatory markers (disintegrin and metallopeptidase domain, morphogenetic protein 8a, and neuregulin 4), and improves angiogenesis (vascular endothelial growth factor A, and perlecan). In addition, cotadutide enhances lipolysis (perilipin and cell death-inducing DNA fragmentation factor α), mitochondrial biogenesis (nuclear respiratory factor 1, transcription factor A mitochondrial, mitochondrial dynamin-like GTPase, and peroxisome proliferator-activated receptor gamma coactivator 1α), and mitochondrial fusion/fission (dynamin-related protein 1, mitochondrial fission protein 1, and parkin RBR E3 ubiquitin protein ligase). Cotadutide reduces endoplasmic reticulum stress (activating transcription factor 4, C/EBP homologous protein, and growth arrest and DNA-damage inducible), and extracellular matrix markers (lysyl oxidase, collagen type I α1, collagen type VI α3, matrix metallopeptidases 2 and 9, and hyaluronan synthases 1 and 2). In conclusion, the experimental evidence is compelling in demonstrating cotadutide's thermogenic effect on obese mice's iBAT, contributing to unraveling its action mechanisms and the possible translational benefits.


Assuntos
Tecido Adiposo Marrom , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Masculino , Tecido Adiposo Marrom/metabolismo , Camundongos Obesos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Adipócitos Marrons , Dieta Hiperlipídica/efeitos adversos , Termogênese , Dinaminas/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
8.
Adv Exp Med Biol ; 1408: 183-199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37093428

RESUMO

Muscle atrophy decreases muscle mass with the subsequent loss of muscle function. Among the mechanisms that trigger sarcopenia is mitochondrial dysfunction. Mitochondria, whose primary function is to produce ATP, are dynamic organelles that present the process of formation (mitogenesis) and elimination (mitophagy). Failure of any of these processes contributes to mitochondrial malfunction. Mitogenesis is mainly controlled by Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), a transcriptional coactivator that regulates the expression of TFAM, which participates in mitogenesis. Mitophagy is a process of selective autophagy. Autophagy corresponds to a degradative pathway of protein complexes and organelles. Liver disease caused sarcopenia and increased bile acids in the blood. We demonstrated that the treatment with cholic (CA) or deoxycholic (DCA) bile acids generates mitochondrial dysfunction and loss of biomass. This work assessed whether CA and DCA alter autophagy and mitogenesis. For this, western blot evaluated the autophagy process by determining the protein levels of the LC3II/LC3I ratio. In addition, we assessed mitogenesis using a luciferase-coupled plasmid reporter for the PGC-1α promoter and the protein levels of TFAM by western blot. Our results indicate that treatment with CA or DCA induces autophagy, represented by an increase in the LC3II/LC3I ratio. In addition, a decreased autophagic flux was observed. On the other hand, when treated with CA or DCA, a decrease in the activity of the PGC-1α promoter was observed. However, the levels of TFAM increased in myotubes incubated with CA and DCA. Our results demonstrate that CA and DCA modulate autophagy ad mitogenesis in C2C12 myotubes.


Assuntos
Doenças Musculares , Sarcopenia , Humanos , Músculo Esquelético/metabolismo , Sarcopenia/patologia , Ácidos e Sais Biliares , Fibras Musculares Esqueléticas/metabolismo , Autofagia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
9.
Nutrients ; 15(5)2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36904162

RESUMO

Dietary regimens that are focused on diminishing total caloric intake and restricting palatable food ingestion are the most common strategies for weight control. However, restrictive diet therapies have low adherence rates in obese patients, particularly in stressed individuals. Moreover, food restriction downregulates the hypothalamic-pituitary-thyroid axis (HPT) function, hindering weight loss. Intermittent fasting (IF) has emerged as an option to treat obesity. We compared the effects of IF to an all-day feeding schedule on palatable diet (PD)-stress (S)-induced hyperphagia, HPT axis function, accumbal thyrotropin-releasing hormone (TRH), and dopamine D2 receptor expression in association with adipocyte size and PPARƔ coactivator 1α (PGC1α) and uncoupling protein 1 (UCP1) expression in stressed vs. non-stressed rats. After 5 weeks, S-PD rats showed an increased energy intake and adipocyte size, fewer beige cells, and HPT axis deceleration-associated low PGC1α and UCP1 expression, as well as decreased accumbal TRH and D2 expression. Interestingly, IF reversed those parameters to control values and increased the number of beige adipocytes, UCP1, and PGC1α mRNAs, which may favor a greater energy expenditure and a reduced body weight, even in stressed rats. Our results showed that IF modulated the limbic dopaminergic and TRHergic systems that regulate feeding and HPT axis function, which controls the metabolic rate, supporting this regimen as a suitable non-pharmacologic strategy to treat obesity, even in stressed individuals.


Assuntos
Sistema Hipotálamo-Hipofisário , Glândula Tireoide , Ratos , Animais , Glândula Tireoide/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Jejum Intermitente , Hormônio Liberador de Tireotropina , Peso Corporal , Obesidade/metabolismo , Ingestão de Alimentos
10.
Cells ; 12(3)2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36766827

RESUMO

Mitochondrial activity and quality control are essential for neuronal homeostasis as neurons rely on glucose oxidative metabolism. The ketone body, D-ß-hydroxybutyrate (D-BHB), is metabolized to acetyl-CoA in brain mitochondria and used as an energy fuel alternative to glucose. We have previously reported that D-BHB sustains ATP production and stimulates the autophagic flux under glucose deprivation in neurons; however, the effects of D-BHB on mitochondrial turnover under physiological conditions are still unknown. Sirtuins (SIRTs) are NAD+-activated protein deacetylases involved in the regulation of mitochondrial biogenesis and mitophagy through the activation of transcription factors FOXO1, FOXO3a, TFEB and PGC1α coactivator. Here, we aimed to investigate the effect of D-BHB on mitochondrial turnover in cultured neurons and the mechanisms involved. Results show that D-BHB increased mitochondrial membrane potential and regulated the NAD+/NADH ratio. D-BHB enhanced FOXO1, FOXO3a and PGC1α nuclear levels in an SIRT2-dependent manner and stimulated autophagy, mitophagy and mitochondrial biogenesis. These effects increased neuronal resistance to energy stress. D-BHB also stimulated the autophagic-lysosomal pathway through AMPK activation and TFEB-mediated lysosomal biogenesis. Upregulation of SIRT2, FOXOs, PGC1α and TFEB was confirmed in the brain of ketogenic diet (KD)-treated mice. Altogether, the results identify SIRT2, for the first time, as a target of D-BHB in neurons, which is involved in the regulation of autophagy/mitophagy and mitochondrial quality control.


Assuntos
NAD , Sirtuína 2 , Animais , Camundongos , Ácido 3-Hidroxibutírico/farmacologia , Ácido 3-Hidroxibutírico/metabolismo , Autofagia , Glucose/metabolismo , Corpos Cetônicos/metabolismo , Corpos Cetônicos/farmacologia , Lisossomos/metabolismo , Mitocôndrias/metabolismo , NAD/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 2/metabolismo
11.
Mol Cell Biochem ; 478(6): 1205-1216, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36272012

RESUMO

Aging is intrinsically related to metabolic changes and characterized by the accumulation of oxidative and inflammatory damage, as well as alterations in gene expression and activity of several signaling pathways, which in turn impact on homeostatic responses of the body. Hypothalamus is a brain region most related to these responses, and increasing evidence has highlighted a critical role of astrocytes in hypothalamic homeostatic functions, particularly during aging process. The purpose of this study was to investigate the in vitro effects of a chronic treatment with resveratrol (1 µM during 15 days, which was replaced once every 3 days), a recognized anti-inflammatory and antioxidant molecule, in primary hypothalamic astrocyte cultures obtained from aged rats (24 months old). We observed that aging process changes metabolic, oxidative, inflammatory, and senescence parameters, as well as glial markers, while long-term resveratrol treatment prevented these effects. In addition, resveratrol upregulated key signaling pathways associated with cellular homeostasis, including adenosine receptors, nuclear factor erythroid-derived 2-like 2 (Nrf2), heme oxygenase 1 (HO-1), sirtuin 1 (SIRT1), proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and phosphoinositide 3-kinase (PI3K). Our data corroborate the glioprotective effect of resveratrol in aged hypothalamic astrocytes, reinforcing the beneficial role of resveratrol in the aging process.


Assuntos
Astrócitos , Fosfatidilinositol 3-Quinases , Ratos , Animais , Resveratrol/farmacologia , Astrócitos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células Cultivadas , Hipotálamo/metabolismo , Sirtuína 1/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/farmacologia
12.
Int J Mol Sci ; 25(1)2023 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-38203446

RESUMO

Lifestyle changes regarding diet composition and exercise training have been widely used as a non-pharmacological clinical strategy in the treatment of obesity, a complex and difficult-to-control disease. Taking the potential of exercise in the browning process and in increasing thermogenesis into account, the aim of this paper was to evaluate the effect of resistance, aerobic, and combination training on markers of browning of white adipose tissue from rats with obesity who were switched to a balanced diet with normal calorie intake. Different types of training groups promote a reduction in the adipose tissue and delta mass compared to the sedentary high-fat diet group (HS). Interestingly, irisin in adipose tissues was higher in the resistance exercise (RE) and aerobic exercise (AE) groups compared to control groups. Moreover, in adipose tissue, the fibroblast growth factor 21 (FGF21), coactivator 1 α (PGC1α), and peroxisome proliferator-activated receptor gamma (PPARγ) were higher in response to resistance training RE compared with the control groups, respectively. Additionally, uncoupling protein 1 (UCP1) showed higher levels in response to group AE compared to the HS group. In conclusion, the browning process in white adipose tissue responds differently toward different training exercise protocols, with resistance and aerobic training efficient in activating different biomarkers of the browning process, upregulating irisin, FGF21, PGC1α, PPARγ, and UCP1 in WAT, which together may suggest an improvement in the thermogenic process in the adipose tissue. Considering the experimental conditions of the present investigation, we suggest future research to pave new avenues to be applied in clinical practices to combat obesity.


Assuntos
Fibronectinas , PPAR gama , Animais , Ratos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Obesidade/terapia , Tecido Adiposo , Proteína Desacopladora 1
13.
Clin Nutr ESPEN ; 51: 1-6, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36184193

RESUMO

Caffeine is one of the most widely used substances as recreational drug for performance-enhancement in sport, underpinned by a strong evidence base. Although the effects of caffeine are widely investigated within the scope of performance physiology, the molecular effects of caffeine within skeletal muscle remain unclear. Evidence from in vitro and in vivo models suggest that caffeine regulates the glucose metabolism in the skeletal muscle. Moreover, caffeine seems to stimulate CaMKII, PPARδ/ß, AMPK and PGC1α, classical markers of exercise-adaptations, including mitochondrial biogenesis and mitochondrial content. This review summarizes evidence to suggest caffeine-effects within skeletal muscle fibers, focusing on the putative role of caffeine on mitochondrial biogenesis to explore whether caffeine supplementation might be a strategy to enhance mitochondrial biogenesis.


Assuntos
Drogas Ilícitas , PPAR delta , Proteínas Quinases Ativadas por AMP/metabolismo , Cafeína/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/farmacologia , Glucose/metabolismo , Humanos , Drogas Ilícitas/metabolismo , Drogas Ilícitas/farmacologia , Músculo Esquelético/metabolismo , Biogênese de Organelas , PPAR delta/metabolismo , PPAR delta/farmacologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/farmacologia
14.
Medicina (Kaunas) ; 58(10)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36295596

RESUMO

Background and Objectives: Perilipins 1-5 (PLIN) are lipid droplet-associated proteins that participate in regulating lipid storage and metabolism, and the PLIN5 isoform is known to form a nuclear complex with peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) to regulate lipid metabolism gene expression. However, the changes in PLIN isoforms' expression in response to pregnancy-induced cardiac hypertrophy are not thoroughly studied. The aim of this study was to quantify the mRNA expression of PLIN isoforms and PGC-1α along with total triacylglycerol (TAG) and cholesterol levels during late pregnancy and the postpartum period in the rat left ventricle. Materials and Methods: Female Sprague-Dawley rats were divided into three groups: non-pregnant, late pregnancy, and postpartum. The mRNA and protein levels were evaluated using quantitative RT-PCR and Western blotting, respectively. TAG and total cholesterol content were evaluated using commercial colorimetric methods. Results: The expression of mRNAs for PLIN1, 2, and 5 increased during pregnancy and the postpartum period. PGC-1α mRNA and protein expression increased during pregnancy and the postpartum period. Moreover, TAG and total cholesterol increased during pregnancy and returned to basal levels after pregnancy. Conclusions: Our results demonstrate that pregnancy upregulates differentially the expression of PLIN isoforms along with PGC-1α, suggesting that together they might be involved in the regulation of the lipid metabolic shift induced by pregnancy.


Assuntos
Receptores Ativados por Proliferador de Peroxissomo , Fatores de Transcrição , Ratos , Feminino , Animais , Gravidez , Perilipina-1 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Ratos Sprague-Dawley , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Cardiomegalia/genética , Cardiomegalia/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Triglicerídeos , Colesterol
15.
Braz J Med Biol Res ; 55: e11820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35588524

RESUMO

The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise.


Assuntos
Condicionamento Físico Animal , Fatores de Transcrição , Animais , Citrato (si)-Sintase/genética , Citrato (si)-Sintase/metabolismo , Citrato (si)-Sintase/farmacologia , Expressão Gênica , Ácido Láctico/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Condicionamento Físico Animal/fisiologia , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
Inflammation ; 45(5): 1985-1999, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35411498

RESUMO

Cardiomyopathy is a well-known complication of sepsis that may deteriorate when accompanied by obesity. To test this hypothesis we fed C57black/6 male mice for 6 week with a high fat diet (60% energy) and submitted them to endotoxemic shock using E. coli LPS (10 mg/kg). Inflammatory markers (cytokines and adhesion molecules) were determined in plasma and heart tissue, as well as heart mitochondrial biogenesis and function. Obesity markedly shortened the survival rate of mouse after LPS injection and induced a persistent systemic inflammation since TNFα, IL-1ß, IL-6 and resistin plasma levels were higher 24 h after LPS injection. Heart tissue inflammation was significantly higher in obese mice, as detected by elevated mRNA expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNFα). Obese animals presented reduced maximum respiratory rate after LPS injection, however fatty acid oxidation increased in both groups. LPS decreased mitochondrial DNA content and mitochondria biogenesis factors, such as PGC1α and PGC1ß, in both groups, while NRF1 expression was significantly stimulated in obese mice hearts. Mitochondrial fusion/fission balance was only altered by obesity, with no influence of endotoxemia. Obesity accelerated endotoxemia death rate due to higher systemic inflammation and decreased heart mitochondrial respiratory capacity.


Assuntos
Endotoxemia , Animais , Citocinas/metabolismo , DNA Mitocondrial , Endotoxemia/metabolismo , Escherichia coli/metabolismo , Ácidos Graxos , Inflamação , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Obesos , Modelos Teóricos , Obesidade/complicações , Obesidade/metabolismo , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , RNA Mensageiro , Resistina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Int J Sports Med ; 43(7): 632-641, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35180801

RESUMO

Metabolic diseases are associated with hypoestrogenism owing to their lower energy expenditure and consequent imbalance. Physical training promotes energy expenditure through PGC-1α and NRF-1, which are muscle proteins of the oxidative metabolism. However, the influence of physical training on protein expression in individuals with hypoestrogenism remains uncertain. Thus, the aim of this study is to determine the effect of 12 weeks of moderate-intensity swimming training on the muscle expression of PGC-1α, NRF-1, glycogen and triglyceride in ovariectomised rats. OVX and OVX+TR rats were subjected to ovariectomy. The trained animals swam for 30 minutes, 5 days/week, at 80% of the critical load intensity. Soleus was collected to quantify PGC-1α and NRF-1 expressions, while gastrocnemius and gluteus maximus were collected to measure glycogen and triglyceride. Blood glucose was also evaluated. Whereas ovariectomy decreased PGC-1α expression (p<0.05) without altering NRF-1 (p=0.48), physical training increased PGC-1α (p<0.01) and NRF-1 (p<0.05). Ovariectomy reduced glycogen (p<0.05) and triglyceride (p<0.05), whereas physical training increased glycogen (p<0.05) but did not change triglyceride (p=0.06). Ovariectomy increased blood glucose (p<0.01), while physical training reduced it (p<0.01). In summary, 12 weeks of individualized and moderate-intensity training were capable of preventing muscle metabolic consequences caused by ovariectomy.


Assuntos
Músculo Esquelético , Fator 1 Relacionado a NF-E2 , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Condicionamento Físico Animal , Animais , Glicemia/metabolismo , Feminino , Glicogênio/metabolismo , Músculo Esquelético/metabolismo , Fator 1 Relacionado a NF-E2/metabolismo , Ovariectomia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Condicionamento Físico Animal/fisiologia , Ratos , Triglicerídeos/metabolismo
18.
Life Sci ; 291: 120239, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34942163

RESUMO

Aim Investigate whether inheritance of improved skeletal muscle mitochondrial function and its association with glycemic control are multigenerational benefits of exercise. MAIN METHODS: Male Swiss mice were subjected to 8 weeks of endurance training and mated with untrained females. KEY FINDINGS: Trained fathers displayed typical endurance training-induced adaptations. Remarkably, offspring from trained fathers also exhibited higher endurance performance, mitochondrial oxygen consumption, glucose tolerance and insulin sensitivity. However, PGC-1α expression was not increased in the offspring. In the offspring, the expression of the co-repressor NCoR1 was reduced, increasing activation of PGC-1α target genes. These effects correlated with higher DNA methylation at the NCoR1 promoter in both, the sperm of trained fathers and in the skeletal muscle of their offspring. SIGNIFICANCE: Higher skeletal muscle mitochondrial function is inherited by epigenetic de-activation of a key PGC-1α co-repressor.


Assuntos
Mitocôndrias/metabolismo , Condicionamento Físico Animal/fisiologia , Esforço Físico/fisiologia , Animais , Metilação de DNA , Epigênese Genética/genética , Feminino , Masculino , Camundongos , Mitocôndrias/fisiologia , Músculo Esquelético/fisiologia , Correpressor 1 de Receptor Nuclear/metabolismo , Consumo de Oxigênio/fisiologia , Herança Paterna/fisiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/fisiologia , Condicionamento Físico Animal/métodos , RNA Mensageiro/genética
19.
J Nutr Biochem ; 99: 108857, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520852

RESUMO

Nutritional insults early in life have been associated with metabolic diseases in adulthood. We aimed to evaluate the effects of maternal food restriction during the suckling period on metabolism and interscapular brown adipose tissue (iBAT) thermogenically involved proteins in adult rat offspring. Wistar rats underwent food restriction by 50% during the first two-thirds of lactation (FR50 group). Control rats were fed ad libitum throughout lactation (CONT group). At birth, the litter size was adjusted to eight pups, and weaning was performed at 22 days old. Body weight and food and water intake were assessed every two days. High- (HCD, 4,589 cal) and normal-caloric diet (NCD, 3,860 cal) preferences, as well as food intake during the dark part of the cycle, were assessed. At 100 days old, the rats were euthanized, and blood and tissues were removed for further analyses. Adult FR50 rats, although hyperphagic and preferring to eat HCD (P<.001), were leaner (P<.001) than the CONT group. The FR50 rats, were normoglycemic (P=.962) and had hypertriglyceridemia (P<.01). In addition, the FR50 rats were dyslipidemic (P<.01), presenting with a high atherogenic risk by the Castelli indexes (P<.01), had a higher iBAT mass (P<.01), fewer ß3 adrenergic receptors (ß3-AR, P<.05) and higher iBAT expression of uncoupled protein 1 (UCP1, P<.05) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, P<.001) than the CONT rats. In conclusion, maternal food restriction during early breastfeeding programs rat offspring to have a lean phenotype, despite hyperphagia, and increased iBAT UCP1 and PGC-1α protein expression.


Assuntos
Tecido Adiposo Marrom/metabolismo , Aleitamento Materno , Lactação/metabolismo , Termogênese , Magreza/metabolismo , Animais , Restrição Calórica , Metabolismo Energético , Feminino , Humanos , Masculino , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fenótipo , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 3/genética , Receptores Adrenérgicos beta 3/metabolismo , Magreza/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
20.
Biochem Genet ; 59(6): 1666-1679, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34057646

RESUMO

Obesity and overweight are worldwide public health problems with an evident genetic predisposition that is still poorly understood. In addition, great variability has been described across populations. In this work, we analyzed the association of variants in four genes: PPARG (rs1801282), PPARGC1A (rs8192678), FTO (rs9939609) and MC4R (rs17782313) with overweight and obesity in a large sample of the Brazilian population. The case-control study involved 4084 individuals (1844 with overweight or obesity; and 2240 with normal BMI). Genotyping was performed by quantitative PCR. MC4R rs17782313-C was associated with obesity (OR = 1.27, p = 0.038) and when stratifying by sex associated only in women (OR = 1.36, p = 0.030). FTO rs9939609-A allele was associated with overweight however for women it represented a risk factor (OR = 1.24, p = 0.034) and for men, a protective factor (OR = 0.68, p = 0.033). PPARG was the strongest associated gene, with both overweight and obesity, and this association was also restricted to women (rs1801282-GG OR = 1.46, p = 0.027). The combined effect of the three risk alleles on overweight and obesity had an OR of 1.65 (p = 0.008) and when stratifying by sex again it was significant only in females (OR = 1.95, p = 0.0028). Our findings indicate that the three genes play a significant role in predisposing to overweight and/or obesity in the Brazilian population, reaching together a relatively high impact on these traits. Interestingly our results also suggest a strong sex-specific genetic effect of these variants.


Assuntos
Sobrepeso , PPAR gama , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Obesidade/genética , Sobrepeso/genética , PPAR gama/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Polimorfismo de Nucleotídeo Único , Receptor Tipo 4 de Melanocortina/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA