title: Intracerebroventricular injection of metformin induces anorexia in rats.
abstract: BACKGROUND
  Metformin, an oral biguanide insulin-sensitizing agent, is well known to decrease appetite. Although there is evidence that metformin could affect the brain directly, the exact mechanism is not yet known.
  
  
  METHODS
  To evaluate whether metformin induces anorexia via the hypothalamus, various concentrations of metformin were injected into the lateral ventricle of rats through a chronically implanted catheter and food intake was measured for 24 hours. The hypothalamic neuropeptides associated with regulation of food intake were also analyzed following 1 hour of intracerebroventricular (ICV) injections of metformin.
  
  
  RESULTS
  An ICV injection of metformin decreased food intake in a dose-dependent manner in unrestrained conscious rats. Hypothalamic phosphorylated AMP-activated protein kinase (pAMPK) increased by 3 µg with metformin treatment, but there was no further increase in pAMPK with increases in metformin dosage. The hypothalamic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased by 3 µg with metformin treatment, but, there was no further increase in pSTAT3 level following increases of metformin dosage. Hypothalamic proopiomelanocortin was elevated with metformin treatment, while neuropeptide Y was not significantly changed.
  
  
  CONCLUSIONS
  Our results suggest that metformin induces anorexia via direct action in the hypothalamus and the increase in pSTAT3, at least in part, is involved in the process. However, hypothalamic pAMPK appears not to contribute to metformin-induced appetite reduction in normal rats. Further studies exploring new pathways connecting metformin and feeding regulation are needed.
authors.affiliation: Department of Physiology, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Chang Koo
authors.initials: CK
authors.lastname: Lee
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.forename: Jong Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Kyu Chang
authors.initials: KC
authors.lastname: Won
authors.forename: Yong Woon
authors.initials: YW
authors.lastname: Kim