title: Acute oral metformin enhances satiation and activates brainstem nesfatinergic neurons.
abstract: OBJECTIVE
  The study was designed to determine metformin effects on meal pattern, gastric emptying, energy expenditure, and to identify metformin-sensitive neurons and their phenotype.
  
  
  METHODS
  This study was performed on C57BL/6J and obese/diabetic (db/db) mice. Metformin (300 mg/kg) was administered by oral gavage. Food intake, meal pattern, oxygen consumption (VO2 ), and carbon dioxide production (VCO2 ) were obtained using an Oxylet Physiocage System. Gastric emptying assay and real-time RT-PCR from dorsal vagal complex extracts were also performed. C-Fos expression was used as a marker of neuronal activation. Phenotypic characterization of activated neurons was performed using either proopiomelanocortin (POMC)-Tau-Topaz GFP transgenic mice or NUCB2/nesfatin-1 and tyrosine hydroxylase (TH) labeling.
  
  
  RESULTS
  Acute per os metformin treatment slowed down gastric emptying, reduced meal size, but not meal number in a leptin-independent manner, and transiently decreased energy expenditure in a leptin-dependent manner. Metformin specifically activated central circuitry within the brainstem, independently of vagal afferents. Finally, while POMC neurons seemed sparsely activated, we report that a high proportion of the c-Fos positive cells were nesfatinergic neurons, some of which coexpressing TH.
  
  
  CONCLUSIONS
  Altogether, these results show that metformin modifies satiation by activating brainstem circuitry and suggest that NUCB2/nesfatin-1 could be involved in this metformin effect.
authors.affiliation: EA 4674, Laboratoire de Physiologie et Physiopathologie du Système Nerveux Somato-Moteur et Neurovégétatif, FST St Jérôme, Aix-Marseille Université, Marseille, France; Biomeostasis CRO, FST St Jérôme, Marseille, France.
authors.forename: Thaïs
authors.initials: T
authors.lastname: Rouquet
authors.forename: Pierre
authors.initials: P
authors.lastname: Clément
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gaigé
authors.forename: Catherine
authors.initials: C
authors.lastname: Tardivel
authors.forename: Julien
authors.initials: J
authors.lastname: Roux
authors.forename: Michel
authors.initials: M
authors.lastname: Dallaporta
authors.forename: Bruno
authors.initials: B
authors.lastname: Bariohay
authors.forename: Jean-Denis
authors.initials: JD
authors.lastname: Troadec
authors.forename: Bruno
authors.initials: B
authors.lastname: Lebrun
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012527:Satiation / Q000187:drug effects*; D013649:Taste / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D008687:Metformin
keywords: NUCB2/nesfatin-1; POMC; c-Fos; db/db mice; energy expenditure; metformin