Central regulation of sympathetic nerve activity by adipokines and insulin

Leptin, resistin and insulin are hormones that circulate in the blood and cross the blood brain barrier. In the brain, they are thought to activate specific regions, which play important roles in energy homeostasis and cardiovascular regulation. The plasma levels of these hormones have been shown to be elevated in overweight and obese conditions, and an increased sympathetic nerve activity (SNA) is also observed in these conditions. In addition, leptin, resistin and insulin plasma levels are strongly correlated with increases in blood pressure suggesting that these hormones may have cardiovascular effects. In high fat diet (HFD), the effects of leptin on renal sympathetic nerve activity (RSNA) are well known. However, the effects of insulin are little known, and the effects of resistin are not known. Since leptin, resistin and insulin levels are increased significantly in obesity and each of these hormones alone can increase RSNA, the question arises as to whether there is an interaction between these hormones on cardiovascular regulation. Thus, the general aim of this thesis was to compare the effects of leptin, resistin and insulin alone and in combination on RSNA, mean arterial pressure (MAP) and heart rate (HR) in rats fed a normal chow diet (ND) or HFD. Male Sprague-Dawley rats were fed a ND and HFD for approximately 8-10 weeks. Saline (5 µl), leptin (7 µg/5 µl), resistin (7 µg/5 µl) and insulin (500 mU/5 µl) were administered intracerebroventricularly (ICV) and RSNA, MAP and HR were monitored and recorded before and for 3 hours after the drug administration. We found that ICV administration of the interaction of (leptin + resistin) increases SNA to the kidney in ND and HFD animals. The effects of leptin and insulin in combination showed that HFD significantly reduced the RSNA responses induced by these hormones in contrast to the increases seen in ND. When resistin and insulin were combined, the response to RSNA was not increased in ND and this effect in HFD, RSNA fell markedly. Together, these data suggest that in HFD the presence of insulin with resistin or leptin may result in a negative interaction on RSNA. However, the positive interaction in HFD seen between resistin and leptin might overcome any negative interaction between insulin with resistin or leptin. Therefore, the interaction between leptin and resistin might be implicated in the abnormal elevation RSNA, seen in overweight /obese conditions.