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1.
Biochem Biophys Res Commun ; 607: 20-27, 2022 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-35366539

RESUMO

Plasma glucose levels are homeostatically regulated within strict boundaries and are maintained through a balance between peripheral glucose uptake and hepatic glucose production. However, little is known about the regulatory mechanism of glucose uptake in adipocytes during fasting. Under fasting conditions, the expression levels of 8 glycolytic enzymes were significantly reduced in adipose tissue. Among them, we focused on lactate dehydrogenase A (LDHA), the last enzyme of the glycolytic pathway. Under fasting conditions, both LDHA and Glut1 protein levels tended to decrease in adipose tissue. To elucidate the significance of LDHA in adipocytes, we generated adipocyte-specific LDHA knockout mice (AdLDHAKO) for the first time. AdLDHAKO mice showed no apparent changes in body weight or tissue weight. Under fasting conditions, AdLDHAKO mice exhibited a significant reduction in Glut1 protein levels and glucose uptake in adipose tissues compared with control mice. Similarly, siRNA of LDHA in 3T3-L1 adipocytes reduced Glut1 protein levels and basal glucose uptake. Moreover, treatment with bafilomycin A1, an inhibitor of lysosomal protein degradation, restored Glut1 protein levels by siRNA of LDHA. These results indicate that LDHA regulates Glut1 expression and basal glucose uptake in adipocytes.


Assuntos
Adipócitos , L-Lactato Desidrogenase , Adipócitos/metabolismo , Animais , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Insulina/metabolismo , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5 , Camundongos , RNA Interferente Pequeno/metabolismo
2.
Biochem Biophys Res Commun ; 585: 155-161, 2021 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-34801935

RESUMO

Glutamine is the most abundant amino acid in the body, and adipose tissue is one of the glutamine-producing organs. Glutamine has important and unique metabolic functions; however, its effects in adipocytes are still unclear. 3T3-L1 adipocytes produced and secreted glutamine dependent on glutamine synthetase, but preadipocytes did not. The inhibition of glutamine synthetase by l-methionine sulfoximine (MSO) impaired the differentiation of preadipocytes to mature adipocytes, and this inhibitory effect of MSO was rescued by exogenous glutamine supplementation. Glutamine concentrations were low, and Atgl gene expression was high in epididymal white adipose tissues of fasting mice in vivo. In 3T3-L1 adipocytes, glutamine deprivation induced Atgl expression and increased glycerol concentration in culture medium. Atgl expression is regulated by FoxO1, and glutamine deprivation reduced FoxO1 phosphorylation (Ser256), indicating the activation of FoxO1. These results demonstrate that glutamine is necessary for the differentiation of preadipocytes and regulates lipolysis through FoxO1 in mature adipocytes.


Assuntos
Adipócitos/metabolismo , Diferenciação Celular/fisiologia , Glutamina/deficiência , Lipólise/fisiologia , Células 3T3-L1 , Adipócitos/citologia , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/metabolismo , Animais , Western Blotting , Diferenciação Celular/genética , Células Cultivadas , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Regulação da Expressão Gênica , Glutamato-Amônia Ligase/genética , Glutamato-Amônia Ligase/metabolismo , Glutamina/metabolismo , Lipase/genética , Lipase/metabolismo , Lipólise/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808082

RESUMO

Aldosterone excess is a cardiovascular risk factor. Aldosterone can directly stimulate an electrical remodeling of cardiomyocytes leading to cardiac arrhythmia and hypertrophy. L-type and T-type voltage-gated calcium (Ca2+) channels expression are increased by aldosterone in cardiomyocytes. To further understand the regulation of these channels expression, we studied the role of a transcriptional repressor, the inhibitor of differentiation/DNA binding protein 2 (Id2). We found that aldosterone inhibited the expression of Id2 in neonatal rat cardiomyocytes and in the heart of adult mice. When Id2 was overexpressed in cardiomyocytes, we observed a reduction in the spontaneous action potentials rate and an arrest in aldosterone-stimulated rate increase. Accordingly, Id2 siRNA knockdown increased this rate. We also observed that CaV1.2 (L-type Ca2+ channel) or CaV3.1, and CaV3.2 (T-type Ca2+ channels) mRNA expression levels and Ca2+ currents were affected by Id2 presence. These observations were further corroborated in a heart specific Id2- transgenic mice. Taken together, our results suggest that Id2 functions as a transcriptional repressor for L- and T-type Ca2+ channels, particularly CaV3.1, in cardiomyocytes and its expression is controlled by aldosterone. We propose that Id2 might contributes to a protective mechanism in cardiomyocytes preventing the presence of channels associated with a pathological state.


Assuntos
Aldosterona/farmacologia , Canais de Cálcio Tipo T/metabolismo , Proteína 2 Inibidora de Diferenciação/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Canais de Cálcio Tipo T/genética , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiologia , Proteína 2 Inibidora de Diferenciação/genética , Camundongos Transgênicos , Miócitos Cardíacos/efeitos dos fármacos
4.
Biochem Biophys Res Commun ; 534: 540-546, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33239174

RESUMO

Nanoparticles, i.e., particles with a diameter of ≤100 nm regardless of their composing material, are added to various foods as moisturizers, coloring agents, and preservatives. Silicon dioxide (SiO2, silica) nanoparticles in particular are widely used as food additives. However, the influence of SiO2 nanoparticle oral consumption on intestinal homeostasis remains unclear. The daily intake of 10-nm-sized SiO2 nanoparticles exacerbates dextran sulfate sodium (DSS)-induced colitis, whereas the daily intake of 30-nm-sized SiO2 nanoparticles has no influence on intestinal inflammation. The exacerbation of colitis induced by consuming 10-nm-sized SiO2 nanoparticles was abolished in mice deficient in apoptosis-associated speck-like protein containing a CARD (ASC). Our study indicates that the oral intake of small SiO2 nanoparticles poses a risk for worsening intestinal inflammation through activation of the ASC inflammasome.


Assuntos
Colite/patologia , Aditivos Alimentares/efeitos adversos , Inflamação/patologia , Nanopartículas/efeitos adversos , Dióxido de Silício/efeitos adversos , Administração Oral , Animais , Colite/induzido quimicamente , Sulfato de Dextrana , Aditivos Alimentares/administração & dosagem , Inflamassomos/análise , Inflamação/induzido quimicamente , Intestinos/patologia , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Tamanho da Partícula , Dióxido de Silício/administração & dosagem
5.
J Endocrinol ; 239(1): 63­71, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30307154

RESUMO

Active glucocorticoid levels are elevated in the adipose tissue of obesity due to the enzyme 11 beta-hydroxysteroid dehydrogenase type 1. Glucocorticoids can bind and activate both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and pharmacological blockades of MR prevent high-fat diet-induced obesity and glucose intolerance. To determine the significance of MR in adipocytes, we generated adipocyte-specific MR-knockout mice (AdipoMR-KO) and fed them high-fat/high-sucrose diet. We found that adipocyte-specific deletion of MR did not affect the body weight, fat weight, glucose tolerance or insulin sensitivity. While liver weight was slightly reduced in AdipoMR-KO, there were no significant differences in the mRNA expression levels of genes associated with lipogenesis, lipolysis, adipocytokines and oxidative stress in adipose tissues between the control and AdipoMR-KO mice. The results indicated that MR in mature adipocytes plays a minor role in the regulation of insulin resistance and inflammation in high-fat/high-sucrose diet-induced obese mice.


Assuntos
Adipócitos/metabolismo , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Receptores de Mineralocorticoides/metabolismo , Adipocinas/sangue , Tecido Adiposo/metabolismo , Animais , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Síndrome Metabólica/etiologia , Camundongos Knockout , Obesidade/complicações , Cultura Primária de Células , RNA Mensageiro/metabolismo , Receptores de Mineralocorticoides/genética , Sacarose/efeitos adversos , Triglicerídeos/metabolismo
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