Leptin acts in the rat hypothalamic paraventricular nucleus to induce gastric mucosal damage

Leptin is produced and secreted by adipocytes to regulate body weight homeostasis. Leptin acts centrally to reduce weight by decreasing food intake and increasing energy expenditure. The paraventricular nucleus (PVN) is a central nervous system structure suggested as a site at which leptin acts to exert its central effects. Leptin microinjection (10(-6) M, 0.5 microl) into the PVN of urethan-anesthetized male Sprague-Dawley rats (150-300 g) resulted in significant gastric damage (mean score = 1.75, n = 16). Damage scores were significantly different than those observed after saline microinjection into the PVN (mean score = 0.00, n = 5, P < 0. 05), or leptin microinjection into non-PVN sites (mean score = 0.33, n = 6, P < 0.05). There were no changes in blood pressure (mean area under curve = 401.9 +/- 224.2 mmHg * s, n = 11, P > 0.05) or heart rate (mean area under curve = 40.9 +/- 25.9 beats, n = 10, P > 0.05) in response to leptin microinjection into PVN. These results suggest that leptin acts on a functionally specific population of PVN neurons involved in the control of gastrointestinal function.