RESUMEN
The insulin signaling pathway, involving protein kinase B (PKB) and mitogen-activated protein kinase (MAPK), mediates the biological response to insulin and several growth factors and cytokines. To investigate the correlation between glucose transporter (Glut) biosynthesis and the insulin signaling pathway activated by novel compounds of Liriope platyphylla (LP9M80-H), alterations in Glut and key protein expression in the insulin signaling pathway were analyzed in the liver and brain of ICR mice treated with LP9M80-H. An in vitro assay showed that the highest level of insulin concentration was observed in the LP9M80-H-treated group, followed by the LP-H, LP-M, LP-E, and LP9M80-C-treated groups. Therefore, LP9M80-H was selected for use in studying the detailed mechanism of the insulin signaling pathway in animal systems. In an in vivo experiment, LP9M80-H induced a significant increase in glucose levels and a decrease of insulin concentration in the blood of mice, while their body weight remained constant over 5 days. The expression level of Glut-3 was down-regulated in the liver, or maintained at the same level in the brain of LP9MH80-H-treated mice. These changes corresponded to the phosphorylation of the p38 protein rather than to ERK and JNK in the MAPK signaling pathway. In addition, the expression level of Glut-1 increased significantly after LP9MH80-H treatment of both insulin target tissues in mice. Western blot analysis showed that Akt in the PI3-K pathway mainly participated in Glut-1 biosynthesis. Thus, these results suggest the possibility that the LP9M80-H-induced regulation of Glut-1 and Glut-3 biosynthesis may be mediated by the Akt and p38 MAPK signaling of the insulin signaling pathway in the liver and brain of mice.
Asunto(s)
Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Transportador de Glucosa de Tipo 3/biosíntesis , Insulina/sangre , Liriope (Planta)/química , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Animales , Glucemia/metabolismo , Encéfalo/citología , Encéfalo/metabolismo , Medicamentos Herbarios Chinos/química , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Hígado/citología , Hígado/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Ratones , Ratones Endogámicos ICRRESUMEN
The present study was designed to define how dietary fat type regulates body adiposity in dietary obesity-susceptible (DOS) Sprague-Dawley (SD) rats. Eighty-three SD rats received a purified diet containing 50 g maize oil (MO)/kg for 3 weeks and then thirty-nine of the rats, designated as the DOS rats, were allotted to diets containing 160 g MO (DOS-MO), beef tallow (DOS-BT) or fish oil (DOS-FO)/kg for 9 weeks. As a result of the experiment, the DOS-FO rats had significantly (P<0.05) reduced weight gain and abdominal and epididymal fat-pad mass than the DOS-MO and DOS-BT rats. Serum leptin level was also significantly (P<0.05) lower in the DOS-FO rats; however, hypothalamic leptin receptor (a and b) mRNA and neuropeptide Y expressions were not altered by dietary fat sources. A lower acetyl-CoA carboxylase mRNA expression in the liver was observed in the DOS-FO group, whereas hepatic peroxisome proliferator-activated receptor-gamma mRNA and protein expressions were markedly elevated in the DOS-FO group compared with those in the other groups. We did not observe differences in acetyl-CoA carboxylase and peroxisome proliferator-activated receptor-gamma expressions in epididymal fat of the DOS rats consuming MO, BT or FO. It is concluded from our present observations that dietary fat type, especially that rich in FO, plays a potential role in down-regulation of adiposity by altering hepatic lipogenic genes, rather than feeding behaviour, in the DOS-SD rats.