Exp Clin Endocrinol Diabetes 2014; 122 - P057
DOI: 10.1055/s-0034-1372074

Nicotinamide nucleotide transhydrogenase (NNT) is associated with obesity in mice

A Kunath 1, M Kern 2, JT Heiker 2, G Flehmig 2, A Knigge 2, M Stumvoll 2, M Blüher 2, N Klöting 1
  • 1Leipzig University Medical Center, Integrated Research and Treatment Center for Adiposity Diseases, Leipzig, Germany
  • 2Medical Clinic lll, University of Leipzig, Leipzig, Germany

Background: The C57BL/6JRj and C57BL/6NTac mouse substrains are different in their response to high fat diet induced obesity, despite a homology of 98%. The C57BL/6JRj strain has a mutation in the nicotinamide nucleotide transhydrogenase (NNT) gene. Aim of the study was to examine the role of NNT in high fat diet induced obesity.

Methods: To define the genetic role of the NNT mutation F1 and first backcross hybrids [(C57BL/6JRj x C57BL/6NTac)F1 x C57BL/6NTac] were generated. All backcross hybrids were genetically analyzed by PCR reaction regarding the presence of NNT mutation. The F1 (N = 20, 10 M/10F) and backcross population (N = 190, M97/F93) were fed with a high fat diet (58% fat, Sniff, Soest) for 8 weeks beginning at 4 weeks of age. Body weight, epigonadal and subcutaneous fat mass, as well as insulin-, leptin- and adiponectin levels were measured after 10 weeks of high fat diet and compared to parental strains.

Results: The F1 hybrids revealed an intermediate body weight gain in response to the high fat diet. The backcross hybrids with NNT mutation had significantly less body weight and significantly lower relative fat mass. The serum parameters were unaffected by occurrence of the mutation.

Conclusion: The study shows that the NNT mutation is associated with parameters of obesity in mice.