F-DIO obesity-prone rat is insulin resistant before obesity onset

Barry E. Levin, Christophe Magnan, Stephanie Migrenne, Streamson C. Chua, Ambrose A. Dunn-Meynell

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

We previously created a novel F-DIO rat strain derived by crossing rats selectively bred for the diet-induced obesity (DIO) phenotype with obesity-resistant Fischer F344 rats. The offspring retained the DIO phenotype through 3 backcrosses with F344 rats but also had exaggerated insulin responses to oral glucose before they became obese on a 31% fat high-energy (HE) diet. Here, we demonstrate that chow-fed rats from the subsequent randomly bred progeny required 57% lower glucose infusions to maintain euglycemia during a hyperinsulinemic clamp in association with 45% less insulin-induced hepatic glucose output inhibition and 80% lower insulin-induced glucose uptake than F344 rats. The DIO phenotype and exaggerated insulin response to oral glucose in the nonobese. chow-fed state persisted in the F6 generation. Also, compared with F344 rats, chow-fed F-DIO rats had 68% higher arcuate nucleus proopiomelanocortin mRNA expression which, unlike the increase in F344 rats, was decreased by 26% on HE diet. Further. F-DIO lateral hypothalamic orexin expression was 18% lower than in F344 rats and was increased rather than decreased by HE diet intake. Finally, both maternal obesity and 30% caloric restriction during the third week of gestation produced F-DIO offspring which were heavier and had higher leptin and insulin levels than lean F-DIO dam offspring. Third-gestational week dexamethasone also produced offspring with higher leptin and insulin levels but with lower body weight. Thus F-DIO rats represent a novel and potentially useful model for the study of DIO, insulin resistance, and perinatal factors that influence the development and persistence of obesity.

Original languageEnglish (US)
Pages (from-to)R704-R711
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume289
Issue number3 58-3
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Keywords

  • Development
  • Diabetes
  • Neuropeptide Y
  • Orexin
  • Proopiomelanocortin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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