Master of Science (MS)
The increase in blood levels of GLP-1 with dietary resistant starch is thought to be associated with the activities of hypothalamic NPY/AgRP neurons and the gene expression of glucokinase in the ARC of the hypothalamus. Exendin-4 has been shown to be associated with fatty acid synthesis and oxidation. In this project, it was proposed that 1) food intake will be decreased in GLP-1R KO mice, the glucokinase (GK) mRNA expression in the liver and in the hypothalamus, the hypothalamic NPY mRNA expression will be up-regulated by exendin-4 treatment; and 2) exendin-4 will decrease fatty acid synthesis and increase fatty acid oxidation. In order to investigate these hypotheses, animal experiments were performed. Exendin-4 treated WT and GLP-1R KO mice were injected with exendin-4 at 100µg/Kg body weight or vehicle for 7 days. The exendin-4 treated mice and the vehicle mice were subdivided into fed and fasted groups. There were 8 groups of mice (n=8). Food intake after refeeding at 1h, 2h and 4h was measured. At end of the study, the blood glucose level, the GK, CPT1, AOX1, SCD1, FAS, SREBP1c and PPARã mRNA expressions in liver, and the GK and NPY mRNA expressions in hypothalamus were measured. In this study, the food intake of GLP-1R KO mice at 1h, 2h and 4h was significantly less than in WT mice, and the FAS expression in liver was significantly higher in GLP-1R KO mice than WT mice. Exendin-4 treatment decreased blood glucose, and increased the GK gene expression in liver, but not in the hypothalamus. The food intake and the NPY gene expression were not altered by exendin-4. Only the AOX mRNA expression was increased by exendin-4. CPT1, SCD1, FAS, SREBP1c, and PPARã mRNA were not changed. GLP-1 might have beneficial effects on improving the impairment of nutrient sensing system induced by aging. The up-regulated FAS gene expression might be one possible mechanism for higher body fat in GLP1R KO mice. The lowering body fat storage effect of exendin-4 may be due in part to the increase of the fatty acid oxidation in liver.
Document Availability at the Time of Submission
Release the entire work immediately for access worldwide.
Zhang, Hanjie, "The role of glucagon-like peptide-1 on food intake, glucokinase expression and fatty acid metabolism" (2009). LSU Master's Theses. 3765.
Roy J Martin