title: Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet.
abstract: OBJECTIVE
  Obesity has been suggested to induce selective leptin resistance whereby leptin's anorexic effects are attenuated, whereas the effects to increase sympathetic nervous system activity and blood pressure remain intact. Most studies, however, have tested only the acute responses to leptin administration. This study tested whether feeding a high-fat diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion.
  
  
  METHODS
  Sprague-Dawley rats were fed high-fat diet (40% kcal from fat, n=5) or normal-fat diet (13% kcal from fat, n=5) for a year. Radiotelemeters were implanted for continuous monitoring of mean arterial pressure (MAP) and heart rate (HR). A 21G steel cannula was implanted in the lateral cerebral ventricle [intracerebroventricular (ICV)]. After recovery, leptin was infused ICV at 0.02 μg/kg per min for 10 days.
  
  
  RESULTS
  High-fat rats were heavier than normal-fat rats (582±12 vs. 511±19 g) and exhibited significantly higher MAP (114±3 vs. 96±7 mmHg). Although the acute (24 h) effects of leptin were attenuated in high-fat rats, chronic ICV leptin infusion decreased caloric intake in both groups similarly (50±8 vs. 40±10%) by day 5. Despite decreased food intake and weight loss, leptin infusion significantly increased MAP and HR in both high-fat and normal-fat rats (7±2 and 5±1 mmHg; 18±11 and 21±10 b.p.m., respectively).
  
  
  CONCLUSIONS
  These results suggest that obesity induced by feeding a high-fat diet blunts the acute anorexic effects of leptin but does not cause significant resistance to the chronic central nervous system effects of leptin on appetite, MAP, or HR.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA. jdubinion@umc.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Dubinion
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: da Silva
authors.forename: John E
authors.initials: JE
authors.lastname: Hall
mesh_terms: D000818:Animals; D001066:Appetite; D001794:Blood Pressure; D001835:Body Weight; D004041:Dietary Fats / Q000008:administration & dosage*; D005247:Feeding Behavior; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004041:Dietary Fats; D020738:Leptin