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1.
Mol Nutr Food Res ; 59(6): 1013-24, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25620073

RESUMO

SCOPE: Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. METHODS AND RESULTS: C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1ß, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed. CONCLUSION: Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes.


Assuntos
Fármacos Antiobesidade/farmacologia , Gluconeogênese/efeitos dos fármacos , Resistência à Insulina , Isotiocianatos/farmacologia , Moringa oleifera/química , Aumento de Peso/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Composição Corporal , Colesterol/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica , Fígado Gorduroso/prevenção & controle , Glucose-6-Fosfatase/sangue , Hipoglicemiantes/farmacologia , Insulina/sangue , Interleucina-1beta/sangue , Leptina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Resistina/sangue , Fator de Necrose Tumoral alfa/sangue
2.
J Biol Chem ; 285(7): 4637-44, 2010 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-20018865

RESUMO

To study the metabolic activity of NF-kappaB, we investigated phenotypes of two different mouse models with elevated NF-kappaB activities. The transcriptional activity of NF-kappaB is enhanced either by overexpression of NF-kappaB p65 (RelA) in aP2-p65 mice or inactivation of NF-kappaB p50 (NF-kappaB1) through gene knock-out. In these models, energy expenditure was elevated in day and night time without a change in locomotion. The mice were resistant to adulthood obesity and diet-induced obesity without reduction in food intake. The adipose tissue growth and adipogenesis were inhibited by the elevated NF-kappaB activity. Peroxisome proliferator-activator receptor gamma expression was reduced by NF-kappaB at the transcriptional level. The two models exhibited elevated inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) in adipose tissue and serum. However, insulin sensitivity was not reduced by the inflammation in the mice on a chow diet. On a high fat diet, the mice were protected from insulin resistance. The glucose infusion rate was increased more than 30% in the hyperinsulinemic-euglycemic clamp test. Our data suggest that the transcription factor NF-kappaB promotes energy expenditure and inhibits adipose tissue growth. The two effects lead to prevention of adulthood obesity and dietary obesity. The energy expenditure may lead to disassociation of inflammation with insulin resistance. The study indicates that inflammation may prevent insulin resistance by eliminating lipid accumulation.


Assuntos
Metabolismo Energético/fisiologia , Resistência à Insulina/fisiologia , NF-kappa B/fisiologia , Adipogenia/genética , Adipogenia/fisiologia , Tecido Adiposo Branco/metabolismo , Animais , Western Blotting , Composição Corporal/genética , Composição Corporal/fisiologia , Temperatura Corporal , Peso Corporal/genética , Peso Corporal/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Ingestão de Alimentos/genética , Ingestão de Alimentos/fisiologia , Ensaio de Desvio de Mobilidade Eletroforética , Metabolismo Energético/genética , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Teste de Tolerância a Glucose , Inflamação/genética , Inflamação/metabolismo , Resistência à Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , NF-kappa B/genética , Obesidade/induzido quimicamente , Obesidade/genética , PPAR gama/genética , PPAR gama/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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