Diet-induced obesity increases the frequency of Pig-a mutant erythrocytes in male C57BL/6J mice

J.K. Wickliffe1, S.D. Dertinger2, D.K. Torous2, S.L. Avlasevich2, B.R. Simon-Friedt1, M.J. Wilson1

1 Tulane University
2 Litron Laboratories

Environmental and Molecular Mutagenesis
Volume 57, Issue 9, December 2016, Pages 668–677

Obesity is a well-recognized contributor to cardiovascular disease, osteoarthritis and increased mental health problems (CDC website).  There is also an association between obesity and cancer, although the exact mechanisms of this relationship are not fully understood. Given the increasing prevalence of obesity in the world, it is critical to understand the links between diet, weight and health.
 
Investigators from Tulane University used a mouse model to study the potential impact of obesity on gene mutation.  Mice that are genetically pre-disposed to diet-induced obesity were fed either a high-fat or a normal diet for approximately 6 months. Some animals in each group were challenged with the known mutagenic agent ethylnitrosourea (ENU) and the results were compared to the background levels of mutation and chromosome damage.  Samples were analyzed for micronuclei and Pig-a gene mutation using In Vivo MicroFlow and In Vivo MutaFlow kits, respectively.   
 
Results show there was no difference in background micronucleus frequency between the high and low fat diet groups. However, there was an increase in baseline Pig-a mutation frequency in the high-fat diet group. Both diet groups showed similar increases in Pig-a mutation and micronucleus frequencies when treated with ENU.
 
These results indicate that obesity induced by a high-fat diet elicits changes in physiology that leads to elevated levels of gene mutation. Overall, these experiments suggest "…obesity increases the risk of developing somatic mutation-based diseases such as cancer".

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