Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose ...Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose tissues (WAT) from groups of lean control, high fat diet (HFD), and HFD treated with UP780 were collected for microarray study. Microarray generated gene expression changes were applied to Ingenuity Pathway Analysis for changes in canonical metabolic and signaling pathways. Microarray was validated by quantitative reverse transcriptase-polymerase chain reaction (QPCR), Western blots, liver triglyceride, liver cholesterol, liver steatosis, and insulin ELISA. UP780 treatment decreased liver gene expressions for multiple enzymes involved in fatty acid biosynthesis and triglyceride production. UP780 treatment increased gene expressions globally for the insulin receptor signaling pathway in WAT. Both liver triglyceride and liver cholesterol levels were significantly reduced by UP780 over HFD. The reduction of liver fat was confirmed by microscopic analysis of liver steatosis. Finally, UP780 significantly decreased fasting plasma insulin level over HFD. The mechanism of action for UP780 indicated a reduction of liver fat accumulation and an enhancement in adipose tissue insulin signaling pathway. This provided mechanistic explanation for the in vivo UP780 effects of enhanced insulin sensitiveity and decreased blood glucose in mouse diabetes and prediabetes models.展开更多
文摘Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose tissues (WAT) from groups of lean control, high fat diet (HFD), and HFD treated with UP780 were collected for microarray study. Microarray generated gene expression changes were applied to Ingenuity Pathway Analysis for changes in canonical metabolic and signaling pathways. Microarray was validated by quantitative reverse transcriptase-polymerase chain reaction (QPCR), Western blots, liver triglyceride, liver cholesterol, liver steatosis, and insulin ELISA. UP780 treatment decreased liver gene expressions for multiple enzymes involved in fatty acid biosynthesis and triglyceride production. UP780 treatment increased gene expressions globally for the insulin receptor signaling pathway in WAT. Both liver triglyceride and liver cholesterol levels were significantly reduced by UP780 over HFD. The reduction of liver fat was confirmed by microscopic analysis of liver steatosis. Finally, UP780 significantly decreased fasting plasma insulin level over HFD. The mechanism of action for UP780 indicated a reduction of liver fat accumulation and an enhancement in adipose tissue insulin signaling pathway. This provided mechanistic explanation for the in vivo UP780 effects of enhanced insulin sensitiveity and decreased blood glucose in mouse diabetes and prediabetes models.
