Leptin receptors (ObR) in the forebrain and hindbrain have been independently recognized as important mediators of leptin responses. We recently used low dose leptin infusions to show that chronic activation of both hypothalamic and hindbrain ObR is required to reduce body fat. The objective of this study was to identify the brain nuclei that are selectively activated in rats receiving chronic infusion of leptin in both the forebrain and the hindbrain. Either saline or leptin was infused into 3rd and 4th ventricles (0.1 µg/24h in 3rd, 0.6 µg/24h in 4th) of male Sprague Dawley rats for 6 days using Alzet pumps. Rats infused with leptin into both ventricles (LL) showed a significant increase in pSTAT3 immunoreactivity (pSTAT3-ir) in the arcuate nucleus (Arc), ventromedial (VMH), dorsomedial (DMH) and posterior hypothalamus compared to other groups. No differences in pSTAT3-ir were observed in midbrain or hindbrain nuclei despite a 6 fold higher infusion of leptin into the 4th ventricle than the 3rd. Delta Fos B-ir, a marker of chronic neuronal activation, showed that multiple brain nuclei were chronically activated due to the process of infusion, but only the Arc, VMH, DMH and ventral tuberomamillary nucleus showed a significant increase in LL rats compared to other groups. These data demonstrate that low dose leptin in the hindbrain increases pSTAT3 in areas of the hypothalamus known to respond to leptin, supporting the hypothesis that leptin induced weight loss requires an integrated response from both the hindbrain and forebrain.
- distributed model
- food intake
- body weight
- Copyright © 2014, American Journal of Physiology - Endocrinology and Metabolism