title: Glucagon-like peptide-1 agonist exendin-4 leads to reduction of weight and caloric intake in a rat model of hypothalamic obesity.
abstract: BACKGROUND
  Hypothalamic obesity caused by damage of medial hypothalamic nuclei presents a therapeutic challenge. Glucagon-like peptide-1 agonist exenatide (synthetic version of exendin-4 (Ex4)), used for treatment of diabetes, causes weight loss via hindbrain signaling.
  
  
  METHODS
  We tested Ex4 in an established rat model of medial hypothalamic lesions. Lesion and control animals were administered either daily intraperitoneal injections of 1 µg·kg(-1) Ex4 or saline for 9 days.
  
  
  RESULTS
  In our rat model, a significant difference in percent baseline food intake (lesion -20.8%, control -13.6%; p < 0.001) and percent change in body weight (lesion -4.9%/9 days, control -3.2%/9 days; p < 0.05) was observed during Ex4 treatment compared with saline.
  
  
  CONCLUSIONS
  Ex4 resulted in reduction of food intake and body weight. Follow-up studies are required to further elucidate its effects on energy homeostasis and to establish Ex4 as a potential drug for treatment of hypothalamic obesity.
authors: Seattle Children's Research Institute, Seattle, Wash. 98101, USA.
authors: Clinton T
authors: CT
authors: Elfers
authors: Jill H
authors: JH
authors: Simmons
authors: Christian L
authors: CL
authors: Roth
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D002149:Energy Intake / Q000187:drug effects* / Q000502:physiology; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007027:Hypothalamic Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014688:Venoms / Q000494:pharmacology* / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide