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BACKGROUND: Introducing new goat breeds or transferring adult goats from farms to slaughterhouses requires transportation, which can engender adverse effects, such as oxidative stress, pathological cell apoptosis and autophagy. Current evidence suggests that malondialdehyde (MDA) is a metabolite of lipid peroxidation during oxidative stress, while superoxide dismutase (SOD) and catalase (CAT) can alleviate injury caused by free radicals and reactive oxygen species (ROS). Meanwhile, Bcl-2, Bax, LC3B, PINK1 and Parkin are important proteins that participate in pathological cell apoptosis and autophagy. This study aimed to investigate the effects of transportation stress on oxidative stress indexes and expressions of Bcl-2, Bax, LC3B, PINK1 and Parkin in the small intestine of goats. Twelve healthy adult male goats from western Jiangxi province were randomly divided into control, 2 h transportation stress, and 6 h transportation stress groups (n = 4 per group). RESULTS: Our results showed that MDA in the small intestine significantly increased after transportation, while SOD and CAT activities decreased, with a significantly increased apoptosis rate of the small intestine cells. The jejunum and duodenum exhibited the highest apoptosis rate in the 2 h and 6 h transportation groups, respectively. The expression of apoptosis-related genes Bcl-2 and Bax and their corresponding proteins exhibited varying degrees of down-regulation or up-regulation, while Bcl-2 and Bax genes in the small intestine were upregulated in the 6 h transportation group. In addition, autophagosomes and autophagolysosomes were found in various parts of the small intestine by transmission electron microscopy, and autophagy-related genes LC3B, PINK1 and Parkin were significantly down-regulated in the 2 h group and up-regulated in the 6 h group. CONCLUSIONS: Our results indicate that the contents of MDA, SOD and CAT in the small intestine, the expression of pathologic apoptosis-related genes Bcl-2 and Bax, and autophagy-related genes LC3B, PINK1 and Parkin correlated with stress duration caused by transportation. Moreover, this study provides a foothold for further studies on the mechanism of transportation stress in goats and improving animal welfare.
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Apoptose , Cabras , Masculino , Animais , Proteína X Associada a bcl-2/farmacologia , Cabras/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Autofagia , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo , Jejuno/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/farmacologia , Proteínas QuinasesRESUMO
Sesamol is the major bioactive constituent isolated from sesame seeds and has a variety of bioactivities. However, its role and mechanism in liver insulin resistance remain unknown. The current study was designed to investigate the underlying adipose-liver crosstalk mechanism of sesamol ameliorating hepatic insulin sensitivity. The therapeutic effect of sesamol was evaluated in high-fat diet (HFD)-fed C57BL/6 J mice (100 mg/kg for 8 weeks, XYGW-2021-75) and the mechanism was further explored in HepG2 cells with/without adiponectin and adenosine 5 '-monophosphate-activated protein kinase (AMPK) inhibitor administration. Our in vivo data showed that sesamol reduced hepatic insulin resistance in HFD-induced mice with obesity by modulating protein expression levels of glycogen synthase (GS), phosphoenolpyruvate carboxykinase (PEPCK) and protein kinase B (AKT). Moreover, sesamol not only increased the serum and adipose tissue adiponectin concentrations but also activated the phosphorylation of AMPK in the liver. Furthermore, in vitro studies using recombinant human adiponectin and an AMPK inhibitor revealed that adiponectin and sesamol have a synergic impact on increasing glycogenesis and reducing gluconeogenesis, of which the effects could be attenuated by the AMPK inhibitor. Taken together, our results suggested that sesamol stimulated adiponectin secretion from adipocytes, whereby exhibited a co-effect on activating the downstream signal of hepatic AMPK, resulting in the alleviation of hepatic insulin resistance. The novel findings of sesamol on hepatic effects provides prospective therapeutic approaches to treat insulin resistance.
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Resistência à Insulina , Humanos , Camundongos , Animais , Adiponectina/metabolismo , Adiponectina/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Fígado , Obesidade/tratamento farmacológico , Insulina/metabolismoRESUMO
The aim of the present study was to investigate the pathological injury and the expression of heat shock proteins in the caprine lung, trachea and bronchus under transport stress. 12 healthy male goats were selected and randomly divided into three groups. The control group (non-transported group), 2 hr transport-treated group and 6 hr transport-treated group. Morphological changes as well as the expression of heat shock proteins (HSPs, mainly HSP27, HSP70 and HSP90) in three parts of the respiratory tract were examined. Our results showed swollen mucosa and congestive blood vessels in mucous layer and submucosa, inflammatory cell infiltration as well as degeneration and necrosis of mucosal epithelial cells in trachea and bronchus of the transport-treated groups. The epithelial cells were degenerated, and the exfoliated cells and debris could be seen in the alveolar cavity. The results of immunohistochemistry showed that HSP27 and HSP70 were strongly expressed in tracheal and bronchial epithelium, glandular epithelium, vascular endothelium and bronchiole epithelium. And the amount of positive inflammatory cells was increased in transport-treated groups. Western blot results indicated that the expression of all three proteins had no obvious difference among the three groups in bronchi (p > .05). In trachea, there was no significant difference in the expression of heat shock proteins among the three groups except that the expression of HSP70 which was obviously higher in the two transported groups than the control group (p < .05). The expression level of HSP70 in the 2 hr transport-treated group was significantly higher than the 6 hr group (p < .05) and control groups (p < .05). However, there was no significant difference in the expression level of HSP27 and HSP90 in three groups (p > .05). In conclusion, our data showed that transport stress could damage the caprine respiratory system.
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Cabras , Proteínas de Choque Térmico , Animais , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Masculino , Sistema RespiratórioRESUMO
BACKGROUND: Transportation is necessary to introduce new breeds of goats to the farm and move the adult meat goat from the farm to the slaughterhouse. However, these actions may give rise to transport stress. Heat shock proteins (HSPs) are playing some important regulate roles during transport stress. The aim of this study was to evaluate the effects of transport stress on the pathological injury and HSPs expression in the stomach of goats. A total of three batches of Ganxi goats from western Jiangxi province were enrolled in this study. For each batch, twelve healthy adult male goats were randomly divided into three groups (four goats per batch and per group): Control group, stress group transported during 2 h and stress group transported during 6 h. RESULTS: Our results showed that the different degrees of stomach walls damage, with the change of expression levels of heat shock protein 27 (HSP27), heat shock protein 70 (HSP70) and heat shock protein 90 (HSP90), occurred after goats transportation. In rumen, the mRNA and protein expressions of HSP27 and HSP70 were increased after transport stress, but not HSP90. In reticulum, all three HSPs mRNA and protein levels were upregulated after 2 h transport, but decreased after 6 h transport. In omasum, HSP27 and HSP70 mRNA and protein were increased after transport stress, however, HSP90 mRNA level only had a slightly enhancement after transport stress. In abomasum, HSP70 and HSP90 mRNA and protein levels were increased after transport stress, but HSP27 was decreased after transport stress. CONCLUSIONS: Taken together, these results revealed that the pathological changes in the gastric tissues and the stomach HSPs expression in goats are related to transport stress and duration. Moreover, this study also provides some new data to advocate reducing transport stress of goats and improving animal welfare.
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Cabras/fisiologia , Proteínas de Choque Térmico/metabolismo , Estômago de Ruminante/metabolismo , Estresse Fisiológico , Meios de Transporte , Bem-Estar do Animal , Animais , Proteínas de Choque Térmico/genética , Masculino , RNA Mensageiro/metabolismo , Estômago de Ruminante/patologiaRESUMO
Isoflavones have been reported to stimulate muscle growth. The aim of this in vitro study was to examine anabolic activity and associated molecular mechanisms of a soy extract (SoyEx), isoflavone aglycones, and a mixture simulating the composition of SoyEx in C2C12 myotubes. C2C12 cells were differentiated into myotubes. The effects of SoyEx, genistein, daidzein, glycitein, and the mixture of genistein-daidzein-glycitein (Mix) on myotube diameter and number were determined. In addition, the expression of genes and proteins associated with anabolic activity was analyzed. Treatment with SoyEx, genistein, and Mix led to a significant increase of myotube diameter and an increase of the number of myotubes per area compared to the control cell. The increase of diameter by SoyEx was antagonized by an antiestrogen, not by an antiandrogen. Furthermore, gene expressions of insulin growth factor (IGF)-1 and its receptor (IGF-1R), as well as protein expression of myosin heavy chain (MHC), were significantly increased by SoyEx, genistein, and Mix. The effects induced by genistein and Mix were comparable to SoyEx. In conclusion, SoyEx displays an anabolic activity in C2C12 myotubes by binding to ER and modulating IGF-1 and MHC expression. Our studies with isoflavone aglycones and Mix indicate that the isoflavone aglycone with the highest anabolic bioactivity in SoyEx is genistein.
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Anabolizantes/farmacologia , Glycine max/química , Isoflavonas/farmacologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Mioblastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Quimioterapia Combinada , Genisteína/administração & dosagem , Genisteína/farmacologia , Técnicas In Vitro , Fator de Crescimento Insulin-Like I/metabolismo , Isoflavonas/administração & dosagem , Camundongos , Mioblastos/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Extratos Vegetais/administração & dosagem , Receptor IGF Tipo 1/metabolismoRESUMO
Orf is a zoonosis caused by the Orf virus (ORFV), which is endemic in goats, sheep, and wild ruminants worldwide. Orf infection is prevalent in China, with outbreaks reported in several provinces. Currently, there is limited information available regarding the characterization of ORFV strains in Jiangxi province. This study investigated an acute outbreak of Orf that occurred in 2021 in a goat herd in the Jiangxi province of China. Clinical signs in this case included lesions on the lips, nose, and inside the mouth. The presence of ORFV was confirmed from tissue samples by polymerase chain reaction (PCR). The nucleotide sequences of the B2L and F1L genes were fully sequenced and used to construct phylogenetic trees. The results of this investigation identified the ORFV JXxy2021 as the cause of the outbreak. The phylogenetic analysis revealed that the ORFV strain JXxy2021 had the highest similarity to the ORFV strains GO and FJ-SL from the neighboring province of Fujian. This suggests that JXxy2021 was likely transmitted from Fujian province. The results have provided valuable information on the genetic characteristics of JXxy2021 and the endemic situations of Orf in China.
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The objective of this study was to evaluate the immunomodulatory effects of the purified Ganoderma atrum polysaccharide (PSG-1) on murine macrophage cell line RAW264.7. Phagocytotic assay by fluorescein isothiocyanate-dextran internalization showed that PSG-1 stimulated the phagocytosis of macrophages. G. atrum polysaccharide increased the production of NO, and the level of mRNA expression of inducible nitric oxide synthase in a dose-response manner. G. atrum polysaccharide also dose-dependently induced the release of TNF-α and interleukin-1ß. Generation of reactive oxygen species was promoted by PSG-1, as determined by flow cytometry. Moreover, PSG-1 induced nuclear factor-κB activation by elevation of p65 nuclear translocation, suggesting that PSG-1 probably stimulated macrophage activities by activating the nuclear factor-κB pathway.
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Polissacarídeos Fúngicos/farmacologia , Ganoderma/química , Macrófagos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Animais , Linhagem Celular , Interleucina-1beta/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Genistein (GEN) is one of the most well-known phytoestrogens identified in various legumes. Although increasing evidence shows GEN has a potential use in phytotherapy to regulate lipid metabolism, its therapeutic mechanisms have not yet been completely elucidated, especially epigenetic alterations of miRNAs to alleviate lipid accumulation in the liver remains unknown. PURPOSE: To clarify how GEN modulates the miRNA profile in HepG2 cells and investigate molecular mechanisms of the modulated miRNA on regulating hepatic lipid metabolism. METHODS: The miRNA microarray was performed to compare the miRNAs expression patterns, followed by determining principal miRNA and its target gene associated with hepatic lipid metabolism modulated by GEN. miR-363-3p mimics (mi) and phosphatase and tensin homolog (PTEN)-siRNA were transfected into HepG2 cells and GEN was further treated with the cells for 24 h RESULTS: GEN induced downregulation of miR-363-3p and upregulation of PTEN, which was a target mRNA of miR-363-3p. The miR-363-3p mi led to an upregulation of sterol-regulatory element-binding protein-1c (SREBP-1c) and its downstream lipid synthesis-related factors in HepG2 cells. In addition, the inhibition of PTEN led to an increase of lipogenesis, which was associated with the AKT/mTOR signal regulation. However, GEN treatment could abrogate the lipogenic effects of miR-363-3p mi or PTEN siRNA. The modulation was associated with estrogen receptor ß (ERß). CONCLUSION: We discerned a new mechanism that GEN regulated hepatic lipid metabolism by inhibiting miR-363-3p, which could be mediated via ERß and by targeting PTEN in HepG2 cells. Additionally, GEN reduced hepatic lipid accumulation by regulating PTEN-AKT/mTOR signal. It implicated a protective role of GEN by elucidating its epigenetic modification of the miRNA modulated by ERß on improving hepatic lipid metabolism and provided novel evidence of the mechanism on targeting miR-363-3p/PTEN in treating hepatic lipid disorders.
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Metabolismo dos Lipídeos , MicroRNAs , Humanos , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Genisteína/farmacologia , Células Hep G2 , MicroRNAs/genética , MicroRNAs/metabolismo , Serina-Treonina Quinases TOR/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Interferente Pequeno/metabolismo , LipídeosRESUMO
Sesamol (SEM), a lignan from sesame oil, exhibited potential benefits on obesity treatment by promoting browning of adipocytes, and the current study is aimed to explore the molecular mechanisms of SEM from the aspect of systemic liver-adipose crosstalk that mediated by hepatic fibroblast growth factor 21 (FGF21). Our in vivo data showed that SEM induced energy expenditure and white adipose tissue (WAT) browning by increasing the expression level of uncoupling protein-1 in high fat diet induced obese C57BL/6J mice. Elevated levels of circulating FGF21 associated with the increased expression of hepatic FGF21 were observed after SEM intervention. Simultaneously, the increased adipose fibroblast growth factor tyrosine kinase receptor 1/beta-klotho indicated that FGF21 sensitivity was enhanced by SEM in WAT. Furthermore, our in vitro results from HepG2 and 3T3-L1 cell lines confirmed the effects and revealed the mechanism of SEM on the white adipocytes browning. We found that with the specific inhibitors of PPARα, the SEM-mediated hepatic FGF21 expression was decreased, and with the specific inhibitors of PPARγ, the browning effect of adipocytes by SEM combining with FGF21 was significantly suppressed. Taken together, the mechanism of SEM for inducing the WAT browning might be the modulation of SEM on liver-adipose crosstalk mediated by FGF21, and the PPARs family might be the targets of SEM. The novel findings from the present study provided evidence that SEM could be a potent obesity-treating compound.
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Adipócitos Brancos , Fígado , Camundongos , Animais , Adipócitos Brancos/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Obesidade/metabolismo , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Marrom/metabolismoRESUMO
OBJECTIVE: To explore the application of magnetic resonance imaging (MRI) in the evaluation of radiation-induced sinusitis (RIS), MRI-based scoring system was used to evaluate the development regularity, characteristics and influencing factors of RIS in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: A retrospective analysis was performed by collecting the clinical and MRI data of 346 NPC patients to analyze the characteristics and prognosis of RIS. The predictive model was constructed according to the influencing factors of RIS. RESULTS: (1) In the 2-year follow-up after radiotherapy (RT), there was significant change in L-M score in both groups of NPC patients (sinusitis before RT group: p = 0.000 vs. non-sinusitis before RT group: p = 0.000). After 6 months of RT, the L-M scores of the two groups tended to plateau (sinusitis before RT group: p = 0.311 vs. non-sinusitis before RT group: p = 0.469). (2) The prevalence of sinusitis in two groups of NPC patients (without or with sinusitis before RT) was 83% vs. 93%, 91% vs. 99%, 94% vs. 98% at 1, 6 and 24 months after RT, respectively. (3) In the patients without sinusitis before RT, the incidence of sinusitis in maxillary and anterior/posterior ethmoid, sphenoid and frontal sinuses was 87.1%, 90.0%/87.1%, 49.5%, 11.8% respectively, 1 month after RT. (4) A regression model was established according to the univariate and multivariate analysis of the factors related to RIS (smoking history: p = 0.000, time after RT: p = 0.008 and TNM staging: p = 0.040). CONCLUSION: (1) RIS is a common complication in NPC patients after RT. This disorder progressed within 6 months after RT, stabilized and persisted within 6 months to 2 years. There is a high incidence of maxillary sinus and ethmoid sinus inflammation in NPC patients after RT. (2) Smoking history, time after RT and TNM staging were significant independent risk factors for RIS. (3) The intervention of the risk factors in the model may prevent or reduce the occurrence of RIS in NPC patients.
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Neoplasias Nasofaríngeas , Sinusite , Humanos , Carcinoma Nasofaríngeo/radioterapia , Estudos Retrospectivos , Sinusite/diagnóstico por imagem , Sinusite/etiologia , Imageamento por Ressonância Magnética , Neoplasias Nasofaríngeas/radioterapiaRESUMO
Astragalus membranaceus (AM) is a food and medicinal homologous plant. The current research is aimed to investigate the beneficial effects and mechanisms of AM in treating acquired hyperlipidemia. The network pharmacology and bioinformatics analysis results showed 481 AM-related targets and 474 acquired hyperlipidemia-associated targets, and 101 candidate targets were obtained through the intersection, mainly enriched in endocrine resistance, AGE-RAGE in diabetic complications and p53 signaling pathways. Quercetin, kaempferol, calycosin, formononetin and isorhamnetin were determined as the candidate active components of AM in the treatment of acquired hyperlipidemia. Moreover, key targets of AM, namely, AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), cyclin D1 (CCND1) and estrogen receptor 1 (ESR1), were screened out, which were closely related to adipogenesis, fatty acid metabolism and bile acid metabolism. The subsequent animal experiments showed that AM extract treatment improved the lipid profiles of the high-fat diet (HFD)-fed mice by reducing lipogenesis and increasing lipolysis and lipid ß-oxidation, which were associated with the downregulating of AKT1 and CCND1, and the upregulating of VEGFA and ESR1 in liver and adipose tissue. Overall, AM alleviated acquired hyperlipidemia through regulating lipid metabolism, and AKT1, VEGFA, CCND1 and ESR1 might be the key targets.
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Astragalus propinquus , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas , Hiperlipidemias , Metabolismo dos Lipídeos , Fitoterapia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Liquiritigenin (LQG) is a natural flavonoid from the herb Glycyrrhiza uralensis Fisch that exhibits multiple biological activities. However, its specific role in antiobesity and its related underlying molecular mechanisms remain unknown. The primary purpose of this study is to explore the effects and regulatory mechanisms of LQG on lipid accumulation in 3T3-L1 adipocytes. The results show that LQG significantly reduced triglyceride levels and downregulated the expression of transcription factors such as CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) in 3T3-L1 adipocytes. Additionally, the expression of sterol-regulatory element-binding protein 1c (SREBP1c), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FASN) involved in lipogenesis was reduced by treatment with LQG. The protein expression levels of light chain 3B (LC3B), autophagy-related protein 7 (ATG7) and p62 were also modulated by LQG, leading to the suppression of autophagy. Further, LQG activated the phosphorylation of the mammalian target of rapamycin (mTOR), the inhibition of which was followed by the restored expression of autophagy-related proteins. Pretreatment with an mTOR inhibitor also reverted the expression of several genes or proteins involved in lipid synthesis. These results suggest that LQG inhibited lipid accumulation via mTOR-mediated autophagy in 3T3-L1 white adipocytes, indicating the role of LQG as a potential natural bioactive component for use in dietary supplements for preventing obesity.
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Adipogenia , Metabolismo dos Lipídeos , Células 3T3-L1 , Adipócitos Brancos/metabolismo , Animais , Autofagia , Flavanonas , Lipídeos/farmacologia , Mamíferos/metabolismo , Camundongos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Obesity can evoke changes of skeletal muscle structure and function, which are characterized by the conversion of myofiber from type I to type II, leading to a vicious cycle of metabolic disorders. Reversing the muscle fiber-type conversion in obese states is a novel strategy for treating those with obesity. Sesamol, a food ingredient compound isolated from sesame seeds, exerted potential antiobesity effects. The present research aimed to explore the therapeutic effects of sesamol on obesity-related skeletal muscle-fiber-type conversion and elucidate the underlying molecular mechanisms through utilizing a high-fat-diet-induced obese C57BL/6J mice model and palmitic acid-exposed C2C12 myotubes. The results showed that sesamol attenuated obesity-related metabolic disturbances, elevated exercise endurance of obese mice, and decreased lipid accumulation and insulin resistance in skeletal muscle. After the treatment with sesamol, the muscular mitochondrial content and biogenesis were increased, accompanied by the enzyme activities and myosin heavy-chain isoform changed from type II fiber to type I fiber. Mechanistic studies revealed that the effects of sesamol on reversing skeletal muscle-fiber-type conversion in obese states were associated with the stimulation of the muscular sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) signal pathway, and these effects could be inhibited by a specific inhibitor of SIRT1, EX-527. In conclusion, our research provided novel evidence that sesamol could regulate myofiber-type conversion to treat obesity and obesity-related metabolic disorders by stimulating the muscular SIRT1/AMPK signal pathway.
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Proteínas Quinases Ativadas por AMP , Sirtuína 1 , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Benzodioxóis , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Fenóis , Transdução de Sinais , Sirtuína 1/genética , Sirtuína 1/metabolismoRESUMO
Genistein (GEN) has been shown to significantly inhibit hepatic triglyceride accretion triggered by estrogen deficiency. The main purpose of this in vitro study was to investigate the function and molecular mechanism of estrogen receptor ß (ERß) in regulating hepatic lipid metabolism induced by GEN. Different doses of GEN or GEN with an ERß antagonist were treated with HepG2 cells. Results showed that 25 µM GEN significantly diminished triglyceride levels. Meanwhile, GEN downregulated the levels of genes and proteins involved in lipogenesis, such as sterol-regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and stearoyl-coenzyme A desaturase 1 (SCD1), and upregulated the gene and protein levels of the regulation factors responsible for fatty acid ß-oxidation, such as carnitine palmitoyltransferase 1α (CPT-1α) and peroxisome proliferator-activated receptor α (PPARα). Furthermore, 25 µM GEN reduced the levels of phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Moreover, most of these effects from GEN were reverted by pretreatment with the antagonist of ERß. In conclusion, GEN improved hepatic lipid metabolism by activating ERß and further modulation of Akt/mTOR signals. The results provide novel aspects of the regulatory mechanism of ERß on hepatic lipid metabolism and might help to profoundly understand the functions of food-derived phytoestrogens in preventing and treating hepatic steatosis in postmenopausal women.
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Receptor beta de Estrogênio/metabolismo , Genisteína/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Ácido Graxo Sintase Tipo I/metabolismo , Fígado Gorduroso/tratamento farmacológico , Células Hep G2 , Humanos , Lipogênese , Fígado/metabolismo , PPAR alfa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismoRESUMO
Chronic high-fat diet (HFD) is associated with the onset and progression of hepatic steatosis, and oxidative stress is highly involved in this process. The potential role of sesamol (SEM) against oxidative stress and inflammation at the transcriptional level in a mice model of hepatic steatosis is not known. In this study, we aimed to investigate the scavenging effects of SEM towards reactive oxygen generated by lipid accumulation in the liver of obese mice and to explore the mechanisms of protection. Markers of oxidative stress, vital enzymes involved in stimulating oxidative stress or inflammation, and nuclear transcription of Nrf2 were examined. Our results showed that SEM significantly inhibited the activity of the HFD-induced hepatic enzymes CYP2E1 and NOX2, associated with oxidative stress generation. Additionally, SEM reversed HFD-induced activation of NF-κB, a redox-sensitive transcription factor, and attenuated the expression of hepatic TNF-α, a proinflammatory molecule. Moreover, SEM enhanced HFD-induced hepatic Nrf2 nuclear transcription and increased the levels of its downstream target genes Ho1 and Nqo1, which indicated antiinflammation and antioxidant properties. Our study suggests that chronic HFD led to hepatic steatosis, while SEM exhibited protective effects on the liver by counteracting the oxidative stress and inflammation induced by HFD. The underlying mechanism might involve multiple pathways at the transcriptional level; the antioxidant defense mechanism was in partly mediated by the upregulation of Nrf2.
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Benzodioxóis/farmacologia , Dieta Hiperlipídica/efeitos adversos , Inflamação/prevenção & controle , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Animais , Antioxidantes/farmacologia , Biomarcadores/sangue , Peso Corporal , Ingestão de Energia , Inflamação/induzido quimicamente , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos C57BL , Superóxido Dismutase/sangueRESUMO
BACKGROUND: Obesity is defined as an imbalance between energy intake and expenditure, and it is a serious risk factor of non-communicable diseases. Recently many studies have shown that promoting browning of white adipose tissue (WAT) to increase energy consumption has a great therapeutic potential for obesity. Sesamol, a lignan from sesame oil, had shown potential beneficial functions on obesity treatment. OBJECTIVE: In this study, we used C57BL/6J mice and 3T3-L1 adipocytes to investigate the effects and the fundamental mechanisms of sesamol in enhancing the browning of white adipocytes to ameliorate obesity. METHODS: Sixteen-week-old C57BL/6J male mice were fed high-fat diet (HFD) for 8 weeks to establish the obesity models. Half of the obese mice were administered with sesamol (100 mg/kg body weight [b.w.]/day [d] by gavage for another 8 weeks. Triacylglycerol (TG) and total cholesterol assay kits were used to quantify serum TG and total cholesterol (TC). Oil red O staining was used to detect lipid droplet in vitro. Mito-Tracker Green was used to detect the mitochondrial content. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the levels of beige-specific genes. Immunoblotting was used to detect the proteins involved in beige adipocytes formation. RESULTS: Sesamol decreased the content of body fat and suppressed lipid accumulation in HFD-induced obese mice. In addition, sesamol significantly upregulated uncoupling protein-1 (UCP1) protein in adipose tissue. Further research found that sesamol also significantly activated the browning program in mature 3T3-L1 adipocytes, manifested by the increase in beige-specific genes and proteins. Moreover, sesamol greatly increased mitochondrial biogenesis, as proved by the upregulated protein levels of mitochondrial biogenesis, and the inhibition of the proteins associated with mitophagy. Furthermore, ß3-adrenergic receptor (ß3-AR), protein kinase A-C (PKA-C) and Phospho-protein kinase A (p-PKA) substrate were elevated by sesamol, and these effects were abolished by the pretreatment of antagonists ß3-AR. CONCLUSION: Sesamol promoted browning of white adipocytes by inducing mitochondrial biogenesis and inhibiting mitophagy through the ß3-AR/PKA pathway. This preclinical data promised the potential to consider sesamol as a metabolic modulator of HFD-induced obesity.
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This study aimed to investigate the prevalence of excessive daytime sleepiness (EDS) and explore the association between free sugars intake and EDS. In this cross-sectional study, a total of 1517 middle school students (808 boys and 707 girls) aged 12~14 years were recruited. The study was conducted in Changsha city, China. Adolescents completed an online questionnaire, including the Epworth Sleepiness Scale (ESS), sleep characteristics, a 12-item Food Frequency Questionnaire (FFQ), and other self-reported information. The ESS score ≥ ten was defined as EDS. The anthropometric indices, including height, weight, and waist circumference, were measured and recorded by uniformly trained assistants. Statistical analyses included the Chi-square test and binary logistic regression model. The mean ESS score and free sugars consumption were 6.8 ± 3.9 points and 53.1 ± 44.7 g/d, respectively. The prevalence of EDS among adolescents was 22.5%, and more girls than boys had EDS (26.1% vs. 19.4%, p < 0.05). An exceeded free sugars intake was positively associated with EDS, with the adjusted Odds Ratio (OR) with its 95% Confident Interval (95% CI) of 1.366 (1.060~1.761, p < 0.05). EDS and excessive consumption of free sugars are commonly found among Chinese adolescents. Further studies are needed to confirm whether free sugars restriction can be meaningful to improve daytime drowsiness in those with EDS.
Assuntos
Povo Asiático , Açúcares da Dieta/efeitos adversos , Ingestão de Alimentos , Sono/fisiologia , Adolescente , Criança , China , Feminino , Humanos , Modelos Logísticos , MasculinoRESUMO
A novel divergent domino annulation reaction of prop-2-ynylsulfonium salts with sulfonyl-protected ß-amino ketones has been developed, affording various epoxide-fused 2-methylenepyrrolidines and S-containing pyrroles in moderate to excellent yields. Prop-2-ynylsulfonium salts act as C2 synthons in the reactions providing a promising epoxide-fused skeleton in a single operation with readily accessible starting materials.
RESUMO
Transport stress causes a series of problems to goat production, such as tissue injury and immunity damage. As a pro-survival pathway, the heat shock response protects healthy cells of goat from stressors. To evaluate the effects of transport stress on heat shock protein (HSPs) expression on goat primary parenchymatous organs, a total of three batches of goats were treated in this study. For each batch, 12 healthy adult male goats were randomly and averagely divided into three groups: Control group (non-transported group), 2 hr transported group and 6 hr transported group. Real-time PCR results indicated that the mRNA expression level of heat shock protein 27 (HSP27) in all examined organs of 2 hr transport-treated goats were upregulated (p < .05) except lung, and heat shock protein 70 (HSP70; except spleen) and heat shock protein 90 (HSP90; except liver and lung) were also increased (p < .05). In 6 hr transported group, the transcription levels of HSP27 (except heart and kidney), HSP70 (except heart, liver and lymph nodes) and HSP90 (except heart and spleen) were all backed to the original levels or even reduced (p < .05). Enzyme-linked immunosorbent assay (ELISA) results showed that the protein levels of HSP27 (except lymph nodes), HSP70 (except spleen) and HSP90 (except liver and lung) were all increased after 2 hr transport (p < .05). After 6 hr transport, HSP27 only in kidney and HSP70 only in heart and liver were upregulated (p < .05), while HSP90 in all the examined organs except liver and lung were also maintained in relatively high levels (p < .05). Taken together, these results suggested that the expression of HSPs in goat primary parenchymatous organs may be regulated by transport stress time. Moreover, this study also provides some new data to advocate reducing transport stress of goats and improving animal welfare.
Assuntos
Perfilação da Expressão Gênica/veterinária , Expressão Gênica , Cabras/genética , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP90/genética , Estresse Fisiológico , Criação de Animais Domésticos , Animais , Ensaio de Imunoadsorção Enzimática/veterinária , Cabras/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/veterináriaRESUMO
The purpose of this study was to investigate the combinatory effects of an isoflavone (ISO)-rich diet and exercise on fat mass and lipid metabolism in ovariectomized (OVX) rats. Therefore the female Wistar rats were sedentary, performed an intense treadmill uphill running, received ISOs, or a combination of ISOs and running after ovariectomy. The exercise reduced visceral fat mass, adipocyte size and serum leptin in Sham animals and antagonized the increases of these parameters induced by OVX. ISOs reduced OVX induced increase of serum leptin. The combination of training and ISOs was most effective in reducing serum triglyceride levels. In OVX rats the training stimulated the expression of genes associated with fatty acid synthesis (SREBP-1c and FAS) in adipose tissue, soleus muscle, liver and genes associated with fatty acid oxidation (PPARδ and PGC-1α) in adipose tissue. ISOs stimulated the expression of SREBP-1c and FAS in soleus muscle and PGC-1α in adipose tissue, whereas suppressed hepatic SREBP-1c and FAS expression. Strong additive effects of ISOs combined with the training were observed for PPARδ and PGC-1α expressions in soleus muscle. In conclusion our results demonstrate that both the training and ISOs affect fat mass and fatty acid metabolism in OVX rats. The training seems to have a higher impact than ISO exposure in regulating gene expression in adipose tissue. However, the strongest effects for several of the addressed parameters could be observed in the combination group especially in the soleus muscle. Therefore a combination of training and an ISO-rich diet may have beneficial effects on fatty acid metabolism and could be a concept for the prevention of obesity in postmenopausal females.