Gut Hormones and Appetite Control: A Focus on PYY and GLP-1 as Therapeutic Targets in Obesity

The global obesity epidemic has resulted in significant morbidity and mortality. However, the medical treatment of obesity is limited. Gastric bypass is an effective surgical treatment but carries significant perioperative risks. The gut hormones, peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP-1), are elevated following gastric bypass and have been shown to reduce food intake. They may provide new therapeutic targets. This review article provides an overview of the central control of food intake and the role of PYY and GLP-1 in appetite control. Key translational animal and human studies are reviewed.

demonstration of polyethylenimine mediated gene transfer into the rodent hypothalamus results in persistent over-expression and phenotypic change

Polyethylenimine [PEI] has been proposed as a non-viral vector, and has been successfully used to transfer reporter genes into the central nervous system [CNS], kidneys, and lungs of adult mice. Neuropeptide Y [NPY] is a peptide expressed in the hypothalamus and is important in the regulation of body weight. Using PEI combined with stereotactic microinjection, we have successfully transferred cDNA-encoding NPY driven by the cytomegalovirus [CMV] promoter into the arcuate nucleus of adult male Wistar rats. Animals treated with NPY expressing plasmids [pNPY] gained more weight than the controls [p<0.05], with associated increases in food intake [p<0.05] and decreased brown adipose tissue activity, measured by Guanosine Diphosphate [GDP] binding to mitochondria, [p<0.05]. In a separate study, hypothalamic slices from the rats treated with pNPY/PEI showed increased NPY release [pNPY 9.7 +/- 0.3 fmol/l vs. control 8.3 +/- 0.5 fmol/l, p<0.05, n = 3]. These results suggest that PEI is an effective vector for gene transfer into the rodent brain and can increase the protein production sufficient to result a persistent phenotypic change. This technique offers the potential of a simple and effective method to manipulate gene expression localised to specific regions of the adult rodent brain

Changes in Plasma Leptin Levels Relating to Short-Term Thyroid Manipulation in Rats / 대한내분비학회지

BACKGROUND: Leptin, an adipocyte derived hormone, and thyroid hormone have similar effects on energy homeostasis, such that a shortage of both hormones is associated with decreased energy expenditure and increased body weight. Therefore, for the maintenance of energy homeostasis may require a close interaction between leptin and thyroid hormone. This study was performed to investigate the change in plasma leptin levels relating to short-term thyroid manipulation causing no significant change in body weight. METHODS: Hypothyroidism was induced by surgical thyroidectomy and hyperthyroidism by subcutaneous injection of 50 g of L-T3/100 g body weight/day, for 5 days, in 6~8 weeks old male Wistar rats. Body weights and food intakes were monitored daily until sacrifice. Plasma samples were collected, and the thyroid stimulating hormone (TSH), free triiodothyronine (T3) and leptin levels measured. The plasma leptin levels in rats with hypothyroidism and hyperthyroidism were compared with those of body weights at death and food intakes during the study, atched controls. RESULTS: The rats treated with L-T3 consumed equal amount of food as freely fed, rats but their final body weights were significantly lower (L-T3 treated 220.0 +/- 1.8 vs. freely fed 226.0 +/- 2.0 g, p<0.05). There was no difference in food intake during study, and final body weight, between the thyroidectomised rats and their paired controls (thyroidectomised 220.4 +/- 1.7 vs. paired 223.9 +/- 4.7 g, P=NS). Plasma leptin levels in the L-T3 treated rats were significantly lower than those in freely fed rats (L-T3 treated 1.7 +/- 0.1 vs. freely fed 4.8 +/- 0.2 ng/ml, p<0.005). Conversely, the thyroidectomised rats had higher plasma leptin levels, compared to those of their paired controls (thyroidectomised 4.8 +/- 0.3 vs. paired 1.7 +/- 0.1 ng/ml, p<0.005). CONCLUSION: The Plasma leptin levels in the rats were decreased by short term hyperthyroidism, while they were increased by short term hypothyroidism. These findings suggest that thyroid hormones may affect the production or secretion of leptin