RESUMO
Disruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Here we show that a high-fat diet supplemented with iron reduces body weight gain and hepatic lipid accumulation in mice. Iron supplementation was found to reduce mitochondrial morphological abnormalities and upregulate gene transcription involved in mitochondrial function and beta oxidation in the liver and skeletal muscle. In both these tissues, iron supplementation increased the expression of genes involved in heme or iron-sulfur (Fe-S) cluster synthesis. Heme and Fe-S cluster, which are iron prosthetic groups contained in electron transport chain complex subunits, are essential for mitochondrial respiration. The findings of this study demonstrated that iron regulates mitochondrial signaling pathways-gene transcription of mitochondrial component molecules synthesis and their energy metabolism. Overall, the study elucidates the molecular basis underlying the relationship between iron supplementation and obesity and hepatic steatosis progression, and the role of iron as a signaling molecule.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/tratamento farmacológico , Perfilação da Expressão Gênica/métodos , Ferro/administração & dosagem , Proteínas Mitocondriais/genética , Obesidade/tratamento farmacológico , Animais , Células Cultivadas , Progressão da Doença , Metabolismo Energético/efeitos dos fármacos , Fígado Gorduroso/induzido quimicamente , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/citologia , Ferro/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Obesidade/induzido quimicamente , Análise de Sequência de DNA , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
Asperuloside (ASP) is an iridoid glycoside that is extracted from Eucommia leaves. Eucommia is used in traditional Chinese medicine and has a long history of benefits on health and longevity. Here, we investigated the impact of ASP on obesity-related metabolic disorders and show that ASP reduces body weight gain, glucose intolerance, and insulin resistance effectively in mice fed with a high-fat diet (HFD). Intestinal dysbiosis is closely linked with metabolic disorders. Our data indicate that ASP achieves these benefits on metabolic homeostasis by reversing HFD-induced gut dysbiosis and by changing gut-derived secondary metabolites and metabolic signaling. Our results indicate that ASP may be used to regulate gut microbiota for the treatment of obesity and type 2 diabetes.
RESUMO
Cardiac constructs fabricated using human induced pluripotent stem cells-derived cardiomyocytes (iPSCs-CMs) are useful for evaluating the cardiotoxicity of and cardiac response to new drugs. Previously, we fabricated scaffold-free three-dimensional (3D) tubular cardiac constructs using a bio-3D printer, which can load cardiac spheroids onto a needle array. In this study, we developed a method to measure the contractile force and to evaluate the drug response in cardiac constructs. Specifically, we measured the movement of the needle tip upon contraction of the cardiac constructs on the needle array. The contractile force and beating rate of the cardiac constructs were evaluated by analysing changes in the movement of the needle tip. To evaluate the drug response, contractile properties were measured following treatment with isoproterenol, propranolol, or blebbistatin, in which the movement of the needle tip was increased following isoproterenol treatment, but was decreased following propranolol or blebbistain, treatments. To evaluate cardiotoxicity, contraction and cell viability of the cardiac constructs were measured following doxorubicin treatment. Cell viability was found to decrease with decreasing movement of the needle tip following doxorubicin treatment. Collectively, our results show that this method can aid in evaluating the contractile force of cardiac constructs.
Assuntos
Cardiotoxicidade , Avaliação Pré-Clínica de Medicamentos/métodos , Células-Tronco Pluripotentes Induzidas , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Impressão Tridimensional , Engenharia Tecidual/métodos , Testes de Toxicidade/métodos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/toxicidade , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/toxicidade , Humanos , Isoproterenol/farmacologia , Isoproterenol/toxicidade , Propranolol/farmacologia , Propranolol/toxicidade , Alicerces TeciduaisRESUMO
A high-calorie diet causes fat accumulation and oxidative stress in the liver, leading to fatty liver and eventually non-alcoholic steatohepatitis (NASH). Melon GliSODin® is used as a nutritional supplement because of its antioxidant activity. This study aimed to assess the antioxidant activity of Melon GliSODin® and its effectiveness in preventing NASH, which primarily results from oxidative stress. Furthermore, we verified the protective effect of Melon GliSODin® by administering it to a mouse model of diet-induced NASH. Melon GliSODin® suppressed liver fibrosis and fat accumulation, which is characteristic of the NASH phenotype. Gene expression analysis confirmed the suppression of fat synthesis and activation of antioxidative mechanisms. These results show that Melon GliSODin® mitigates NASH onset at the molecular level, suggesting its potential application as a NASH preventive agent.