BVT.3531 reduces body weight and activates KATP channels in isolated arcuate neurons in rats

A number of hormones, including leptin, have been shown to inhibit food intake in humans and animals. Analogues of 3-guanidinopropionic acid have also been found to reduce total food intake, but their mechanisms of action have not been well studied. The present study investigated the effects of intracerebroventricular infusion of the analogue BVT.3531 on food intake, meal pattern, and body weight in rats during 7 days. Single channel recordings from arcuate neurons and insulinoma cells were used to determine the effects of BVT.3531 on KATP activity. Data analysis showed that BVT.3531 significantly decreased body weight and food intake, primarily by reducing meal size. BVT.3531 activated KATP channels in cell-attached recordings from insulin-secreting cells and rat arcuate neurons but had no effect on KATP channel activity in inside-out membrane patches from either cell type. BVT.3531 did not alter the firing rate or K+ channel activity of arcuate neurons devoid of KATP. The study suggests that small molecules capable of mimicking the effects of leptin on food intake and body weight may utilize output mechanisms similar to those of leptin to elicit changes in arcuate neuron excitability.