Vasopressin and hydration play a major role in the development of glucose intolerance and hepatic steatosis in obese rats

Christopher Taveau, Catherine Chollet, Ludovic Waeckel, Dorinne Desposito, Daniel G. Bichet, Marie-Francoise Arthus, Christophe Magnan, Erwann Philippe, Valerie Paradis, Fabienne Foufelle, Isabelle Hainault, Sofia Enhörning, Gilberto Velho, Ronan Roussel, Lise Bankir, Olle Melander, Nadine Bouby

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/hypothesis 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. Conclusion/interpretation 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.
Original languageEnglish
Pages (from-to)1081-1090
JournalDiabetologia
Volume58
Issue number5
DOIs
Publication statusPublished - 2015

Subject classification (UKÄ)

  • Endocrinology and Diabetes

Free keywords

  • Glucosemetabolism
  • Hydration
  • Lipid metabolism
  • Liver
  • Vasopressin

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