Central leptin infusion attenuates the cardiovascular and metabolic effects of fasting in rats

The role of reduced leptin signaling in the regulation of cardiovascular re sponses to negative energy balance is not known. We tested the hypothesis t hat central infusion of leptin would attenuate the cardiovascular and metab olic responses to fasting, Male Sprague-Dawley rats, instrumented with tele metry devices and intracerebroventricular cannulas, were housed in metaboli c chambers for continuous (24 hours) measurement of dark-phase (active) and light-phase (inactive) mean arterial pressure, heart rate, oxygen consumpt ion, and respiratory quotient. Rats received central infusions of either sa line (0.5 muL/h) or leptin (42 ng/h) for 6 days through osmotic pumps and w ere either fed ad libitum or were fasted for 48 hours followed by refeeding for 4 days. In ad lib animals, continuous intracerebroventricular leptin i nfusion significantly reduced caloric intake, body weight, and respiratory quotient compared with saline controls while having no effect on mean arter ial pressure or heart rate. Fasting reduced mean arterial pressure, heart r ate, oxygen consumption, and respiratory quotient in rats receiving saline infusions. Fasting-induced reductions in mean arterial pressure were specif ic to the active phase and were not attenuated by central leptin infusion. In contrast, intracerebroventricular leptin, at a dose that had no cardiova scular effects in ad lib control animals, completely prevented fasting-indu ced decreases in light-phase heart rate and oxygen consumption and blunted fasting-induced reductions in dark-phase heart rate and oxygen consumption. The results are consistent with the hypothesis that reductions in central leptin signaling contribute to the integrated cardiovascular and metabolic responses to acute caloric deprivation.