RESUMO
Green tea and its major polyphenol epigallocatechin-3-O-gallate (EGCG) have suppressive effect on dietary obesity. However, it remains unsolved what type of diet on which they exhibit high or low anti-obesity effect. In the present study, we investigated whether anti-obesity effect of green tea differs depending on composition of fats or fatty acids that consist high-fat (HF) diet in mouse model. Green tea extract (GTE) intake dramatically suppressed weight gain and fat accumulation induced by olive oil-based HF diet, whereas the effects on those induced by beef tallow-based HF diet were weak. GTE also effectively suppressed obesity induced by unsaturated fatty acid-enriched HF diet with the stronger effect compared with that induced by saturated fatty acid-enriched HF diet. These differences would be associated with the increasing action of GTE on expression of PPARδ signaling pathway-related genes in the white adipose tissue. Expressions of genes relating to EGCG signaling pathway that is critical for exhibition of physiological effects of EGCG were also associated with the different effects of GTE. Here, we show that anti-obesity effect of GTE differs depending on types of fats or fatty acids that consist HF diet and could be attenuated by saturated fatty acid.
Assuntos
Catequina/análogos & derivados , Ácidos Graxos/efeitos adversos , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Chá/química , Tecido Adiposo Branco/patologia , Animais , Catequina/farmacologia , Dieta Hiperlipídica , Masculino , Carne/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Azeite de Oliva/efeitos adversos , PPAR gama/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
Strictinin has been shown to suppress interleukin (IL)-4-induced signal transducer and activator of transcription (STAT)-6 phosphorylation, which is a critical event for IgE class switching. However, it is unclear how strictinin inhibits STAT6 activation. Strictinin inhibited STAT6 phosphorylation by suppressing IL-4 receptor α (IL-4Rα) activation. Strictinin was bound to the cell surface and only localized in non-lipid raft fraction of the cells where IL-4Rα was also located. In addition, strictinin directly bound to IL-4Rα and inhibited binding of IL-4 to IL-4Rα. These results suggest that IL-4Rα locating in non-lipid raft region is a target molecule for strictinin in inhibiting STAT6 activation.
Assuntos
Interleucina-4/metabolismo , Microdomínios da Membrana/metabolismo , Fenóis/farmacologia , Receptores de Interleucina-4/antagonistas & inibidores , Receptores de Interleucina-4/metabolismo , Fator de Transcrição STAT6/metabolismo , Animais , Linfoma de Burkitt , Células HeLa , Humanos , Camundongos , Células NIH 3T3 , Fosforilação/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacosRESUMO
(-)-Epigallocatechin-3-O-gallate (EGCG), a polyphenol in green tea, induces apoptosis in acute myeloid leukemia (AML) cells without affecting normal cells. In this study, we observed that cGMP acts as a cell death mediator of the EGCG-induced anti-AML effect through acid sphingomyelinase activation. EGCG activated the Akt/eNOS axis, a well-known mechanism in vascular cGMP upregulation. We also observed that a major cGMP negative regulator, phosphodiesterase 5, was overexpressed in AML cells, and PDE5 inhibitor, an anti-erectile dysfunction drug, synergistically enhanced the anti-AML effect of EGCG. This combination regimen killed AML cells via overexpressed 67-kDa laminin receptors.