Background. Energy intake in excess of expenditure can lead to obesity and associated co-morbidities. 85% of adults in the United States are projected to be overweight or obese by 2030. The Notch pathway and caloric restriction have both been reported to influence the development of brown adipose tissue (BAT). BAT is associated with increased resting energy expenditure, lower body mass index and may be protective against obesity in rodents and humans. Strategies to increase BAT have been proposed as an approach to reduce obesity. Little is known regarding how caloric restriction may influence Notch expression and subsequent BAT formation. We hypothesized that Notch-4 expression may correlate with caloric restriction and BAT.


Methods. To test this hypothesis, we examined Notch-4 protein expression in the livers of diet-induced obese (DIO) mice that were then subjected to various levels of sustained caloric restriction and/or weight cycling. Notch-4 protein expression was normalized to beta-actin protein expression. We then performed correlation analysis between normalized Notch-4 protein expression and interscapular BAT (iBAT) mass from the same animals.


Results. Spearman correlation revealed that Notch-4 expression had a significant (p=0.02) inverse correlation with iBAT mass. When adjusted for caloric restriction condition, the inverse correlation between Notch-4 and iBAT remained significant (p< 0.01), suggesting that Notch-4 expression is independent of energy intake. Non-parametric analysis of variance with caloric restriction category as the independent variable demonstrated significant differences in iBAT according to caloric restriction condition (p=0.04) but no significant differences in Notch-4 expression (p=0.72).


Conclusions. Our results collectively support a potential role of Notch-4 on iBAT that is independent of energy intake.