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- Title
Diet-induced Obesity in Two C57BL/6 Substrains With Intact or Mutant Nicotinamide Nucleotide Transhydrogenase (Nnt) Gene.
- Authors
Nicholson, Anthony; Reifsnyder, Peter C.; Malcolm, Rachel D.; Lucas, Charlotte A.; MacGregor, Grant R.; Zhang, Weidong; Leiter, Edward H.
- Abstract
The C57BL/6J (B6/J) male mouse represents a standard for diet-induced obesity (DIO) and is unique in expressing a loss-of-function nicotinamide nucleotide transhydrogenase (Nnt) gene. This mutation was associated with a marked reduction in glucose-stimulated insulin secretion from B6/J islets in vitro and moderately impaired glucose clearance in vivo. To assess the contribution of this Nnt mutation, we compared DIO responsiveness of Nnt-mutant B6/J males to Nnt wild-type C57BL/6NJ (B6/NJ) males over a 14-week period of feeding a high-fat (60% of calories) diet. Initial mean body weights at 6 weeks did not distinguish the substrains and both substrains were DIO-sensitive. However, B6/J males outgained the B6/NJ males, with a significant 3 g higher mean body weight at 20 weeks accompanied by significant increases in both lean and fat mass. Mean nonfasting serum glucose over time was also significantly higher in B6/J males, as was impairment of glucose tolerance assessed at 8 and 20 weeks of age. Serum leptin, but not insulin, was significantly higher in B6/J males over time. Potential contributions of the wild-type Nnt gene were demonstrable on a lower fat diet (10% of calories) where a significantly greater weight gain over time by B6/NJ males was correlated with a significantly higher serum insulin. In conclusion, DIO developed in response to 60% fat feeding regardless of Nnt allele status. Contribution of the B6/J-unique Nnt mutation was most evident in response to 10% fat feeding that resulted in reduced serum insulin and weight gain compared to B6/NJ males.
- Subjects
OBESITY; LABORATORY mice; NUCLEOTIDES; GENES; GENETIC mutation; INSULIN
- Publication
Obesity (19307381), 2010, Vol 18, Issue 10, p1902
- ISSN
1930-7381
- Publication type
Article
- DOI
10.1038/oby.2009.477