PAI-1 and the Diet-Induced Obesity Phenotype: Background Effects and Inbreeding pp.183-198
Authors: (Bart M. De Taeye, Tatiana Novitskaya, and Douglas E. Vaughan, Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN)
Abstract: The effect of PAI-1 deficiency on the development of obesity and insulin resistance is controversial. Published reports have suggested that PAI-1 deficiency can protect or have no effect on the development of diet-induced obesity in mice. To further investigate these apparent discrepant findings, PAI-1 deficient and wild-type C57BL/6J littermate mice were fed a diet high in fat or a regular diet and this for either 12 or 30 weeks. The development of obesity and the degree of insulin resistance was analyzed. PAI-1 deficient animals were not protected from the development of obesity or insulin resistance. Analysis of the change in weight and percentage body fat for the individual mice revealed that even though mice were littermates, they showed significant variability in the degree of obesity development and adipose tissue accumulation within the same group, in agreement with findings from studies focusing on the effects of epigenetic changes in diet-induced obesity in littermate mice. As such, while our data confirm that PAI-1 genotype does not influence the development of diet-induced obesity and diabetes, they help explaining so far contradicting data. In conclusion, PAI-1 inhibition could be important to prevent complications associated with obesity but not the development of obesity itself.