title: Vasopressin and hydration play a major role in the development of glucose intolerance and hepatic steatosis in obese rats.
abstract: OBJECTIVE
  High plasma copeptin, a marker of vasopressin (VP) secretion, has been shown to be associated with the metabolic syndrome and development of type 2 diabetes in humans. The present study was designed to determine the long-term influence of plasma VP concentration in a rodent model prone to metabolic dysfunction.
  
  
  METHODS
  Obese Zucker rats and their lean counterparts were submitted for 4 weeks to one of three protocols inducing different levels of VP. Circulating VP was either reduced by increasing the daily water intake (low-VP), or increased by a chronic i.p. infusion of VP (high-VP). The control rats had normal VP levels that depended on their own regulation of water intake and VP secretion.
  
  
  RESULTS
  Compared with controls with normal VP, lean rats with high-VP had a higher fasting glycaemia after 4 weeks. In obese rats, high-VP promoted hyperinsulinaemia, glucose intolerance, assessed by glucose and insulin tolerance tests, and an impaired response to a pyruvate challenge. Conversely, treatment with a selective arginine vasopressin receptor 1A (V1aR) antagonist reduced glucose intolerance. Low-VP obese rats had unchanged glucose tolerance but exhibited a drastic decrease in liver steatosis compared with control obese rats, associated with low hepatic triacylglycerol and cholesterol content, and reduced expression of hepatic lipogenic genes. These effects were independent of changes in body adiposity, and plasma sodium and osmolality did not differ among groups.
  
  
  CONCLUSIONS
  These findings show a causal relationship between the VP-hydration axis and the metabolic risk. Therapeutic perspectives include diet recommendations regarding hydration, but also potential pharmacological interventions targeting the VP V1aR.
authors.affiliation: Inserm U1138, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Medecine, 75006, Paris, France.
authors.forename: Christopher
authors.initials: C
authors.lastname: Taveau
authors.forename: Catherine
authors.initials: C
authors.lastname: Chollet
authors.forename: Ludovic
authors.initials: L
authors.lastname: Waeckel
authors.forename: Dorinne
authors.initials: D
authors.lastname: Desposito
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bichet
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Arthus
authors.forename: Christophe
authors.initials: C
authors.lastname: Magnan
authors.forename: Erwann
authors.initials: E
authors.lastname: Philippe
authors.forename: Valerie
authors.initials: V
authors.lastname: Paradis
authors.forename: Fabienne
authors.initials: F
authors.lastname: Foufelle
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hainault
authors.forename: Sofia
authors.initials: S
authors.lastname: Enhorning
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.forename: Lise
authors.initials: L
authors.lastname: Bankir
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.forename: Nadine
authors.initials: N
authors.lastname: Bouby
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D004326:Drinking / Q000502:physiology*; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism; D018149:Glucose Intolerance / Q000209:etiology* / Q000378:metabolism; D005951:Glucose Tolerance Test; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009765:Obesity / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D011924:Rats, Zucker; D014667:Vasopressins / Q000097:blood* / Q000494:pharmacology
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001786:Blood Glucose; D007211:Indoles; D011759:Pyrrolidines; D014667:Vasopressins; C082134:relcovaptan