Sex differences in the response to circadian disruption in diurnal sand rats

Most animal model studies on physiological functions and pathologies are conducted in males. However, diseases such as depression, type 2 diabetes (T2DM) and cardiovascular disease, all show different prevalence and characteristics in females and males. Moreover, most mammal studies are conducted in nocturnal mice and rats, while modelling diurnal humans. We therefore used male and female fat sand rats (Psammomys obesus), which are diurnal in the wild, as an animal model for T2DM, to explore the effects of mild circadian disruption on behavior, glucose tolerance, cholesterol and heart weight. We found significant differences between the sexes: on average, in response to short photoperiods (SP) acclimation, males showed higher levels of depression-like behavior, lower glucose tolerance, and increased plasma cholesterol levels compared with females, with no effect on heart/body weight ratio. Females, however did show an increase in heart/body weight ratio in response to SP acclimation. We also found that regardless of sex, arrhythmic animals showed higher blood glucose levels, cholesterol levels, heart/body weight ratio, and depressive-like behavior compared with rhythmic animals. Hence, we suggest that the expression of the Circadian Syndrome could be different between males and females. Additional work with females is required to clearly delineate the specific effects in both sexes, and promote sex-based health care, prevention measures and therapies.