Nicotinamide Nucleotide Transhydrogenase (Nnt) is Related to Obesity in Mice

The C57BL/6J (B6J) mouse strain has been widely used as a control strain for the study of metabolic diseases and diet induced obesity (DIO). B6J mice carry a spontaneous deletion mutation in the nicotinamide nucleotide transhydrogenase ( Nn ) gene eliminating exons 7-11, resulting in expression of a truncated form of Nn , an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this mutation in B6J mice is associated with epigonadal fat mass and altered sensitivity to diet induced obesity. To define the role of Nn in the development of diet induced obesity, we generated first backcross (BC1) hybrids of wild type Nn C57BL/6NTac and mutated Nn C57BL/6JRj [(C57BL/6NTac×C57BL/6JRj)F1×C57BL/6NTac]. Body weight gain and specific fat-pad depot mass were measured in BC1 hybrids under high fat diet conditions. Both sexes of BC1 hybrids indicate that mice with Nn wild type allele are highly sensitive to DIO and exhibit higher relative fat mass. In summary, our data indicate that the Nn mutation in mice is associated with sensitivity to DIO and fat mass.