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Diet‐induced Obesity in Two C57BL/6 Substrains With Intact or Mutant Nicotinamide Nucleotide Transhydrogenase ( Nnt ) Gene
Author(s) -
Nicholson Anthony,
Reifsnyder Peter C.,
Malcolm Rachel D.,
Lucas Charlotte A.,
MacGregor Grant R.,
Zhang Weidong,
Leiter Edward H.
Publication year - 2010
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2009.477
Subject(s) - endocrinology , medicine , calorie , obesity , insulin , weight loss , leptin , allele , calorie restriction , biology , gene , genetics
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.