| Obesity and high fat diets are associated with the increased risk of diabetes, cardiovascular disease, and hypertension. The mechanism(s) linking obesity and high fat diet to these diseases are unknown. Obesity is associated with increased adipocyte derived leptin and leptin stimulates the hypothalamic proopiomelanocortin (POMC)-derived peptides. The aim of this study was to determine if POMC-derived peptides could play an essential role in linking obesity and cardiovascular dynamics. Both alpha-MSH and beta-endorphins increased cardiovascular and autonomic nervous function. We investigated the effect of a high fat diet on cardiovascular dynamics and physical activity. Male Wistar rats were implanted with radio-telemetry transmitters for continuous recordings of animal's blood pressure, heart rate and physical activity and subsequently implanted with intracerebroventricular (ICV) cannulas in the lateral ventricle of the brain for drug administration. The rats were fed either a high fat diet (HF; 59% fat content) or regular diet (control; 12% fat content). Body weight, food and water intake was determined. We observed that the acute administration of alpha-MSH and beta-END increases MAP and HR, while the chronic infusion of alpha-MSH and beta-END decreases MAP, HR, and physical activity. alpha-MSH decreases food intake and beta-END is associated with stimulation of a short-term increase in food and water intake. High fat fed rats consume more calories and have higher blood pressures. In addition, the mu receptor agonist, DAMGO increased MAP with the chow fed being more sensitive at the lower dose and the HF at the higher dose. The mu antagonist, beta-FNA responded with a decrease only in the chronic study. The mu antagonist, CTAP increased blood pressure in both groups. Thus, these findings suggest that the Leptin-POMC system may play a role in coupling obesity to hypertension. |
