RGD Reference Report - F-DIO obesity-prone rat is insulin resistant before obesity onset. - Rat Genome Database

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

Authors: Levin, Barry E  Magnan, Christophe  Migrenne, Stephanie  Chua, Streamson C  Dunn-Meynell, Ambrose A 
Citation: Levin BE, etal., Am J Physiol Regul Integr Comp Physiol. 2005 Sep;289(3):R704-11. doi: 10.1152/ajpregu.00216.2005. Epub 2005 May 5.
RGD ID: 24922212
Pubmed: (View Article at PubMed) PMID:15879056
DOI: Full-text: DOI:10.1152/ajpregu.00216.2005

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.



Disease Annotations    
obesity  (IAGP)

Phenotype Annotations    
Objects Annotated

Strains
F344  (Fischer)
FDIO/Rrrc  (NA)


Additional Information