# Exosomal miR-92a Concentration in the Serum of Shift Workers
## 4 Discussion  
Shift work may disrupt sleep and meal rhythms. The perturbation of biological rhythms can alter metabolic homeostasis that may lead to weight gain and/or metabolic disturbances [54; 55; 56; 57]. Shift work was associated with higher waist circumference [58; 59; 60], and a higher risk of metabolic syndrome and cardiovascular events [7; 61; 62; 63]. In our sample, SW are similar to DT nurses concerning the waist circumference and the other metabolic parameters analyzed. The lack of differences is likely due to the small size effect that shift work has on metabolic parameters. A larger sampling would help this to be more visible. Moreover, our sample constituted of young nurses (median age of 39.0 years) with a median job seniority of 13.0 years. These parameters likely differ from the metabolic alterations shown in older shift workers [64]. Several authors have obtained increased BMI values in SW compared to DT workers [65; 60; 66], which, however, were not found to be associated to differences in diet style [65; 67], nor in physical activity between the two groups of workers [10; 68; 69]. Other factors, such as a low level of active BAT, may also contribute to weight gain in SW. This study measured the levels of miR-92a that a study of [PERSON] and colleagues inversely correlated with BAT activity [39]. Contrary to the hypothesis that SW may have a low level of active BAT, we found lower levels of miR-92a in SW nurses compared to DT nurses, indicative of higher BAT activity [39]. Several argumentations may be possible: (1) The increased BAT activity detected in SW nurses may be a physiologic mechanism to counteract metabolic alterations induced by circadian disruption linked to shift work. This counteracting mechanism may be impaired after a long duration of shift work resulting in weight gain and metabolic syndrome. (2) In a study on mice, prolonged daily light exposure (similar to the experiences of shift workers during a night shift) decreases BAT activity [70]. However, mice differ from humans as they usually sleep during the day and are active and eat during the night, resulting in a possible opposite effect of light on BAT. (3) Shift work can induce a sympathodominant state [71]. Since the sympathetic nervous system is a stimulator of BAT [72], the higher BAT activity in SW nurses may be caused by a sympathetic stimulation. (4) Since BAT activity has a circadian rhythm [73; 74], our finding may be related to a phase misalignment of a circadian cycle of BAT activity in SW compared to DT nurses. (5) Since the activity of BAT produces heat, its increased activity may be the cause of the higher peripheral skin temperature previously demonstrated in a similar sample of SW nurses [75]. (6) The lower levels of miR-92a found in the serum of shift workers may not only be related to BAT activity, but also to other biological processes [76; 77]. This last hypothesis must be carefully considered. Further investigations are necessary due to the inverse correlation between serum exosomal miR-92a and BAT activity, which is based only on the study of [PERSON] and colleagues [39]. Moreover, the miR-92a is involved in the regulation of several genes. MiRTargetLink [78], using information from miRTarBase [79; 80], found 1419 genes that are targeted by miR-92a: 30 interactions with strong support, 1301 interactions with weak support, and 88 predicted interactions (Table S1). MiR-92a regulates several processes including cell proliferation and the development of cancer [77; 81]. Night shift work has been suggested to be associated with the onset of cancer, specifically breast cancer [82; 83; 84; 85]. Interestingly, in breast cancer the miR-92a is deregulated [86; 87; 88; 89; 90; 91; 92]. The miR-92a targets and downregulates estrogen receptor beta (ER\(\beta\)), and is controlled by estrogen [93]. Since higher levels of estrogen were found in shift workers [94; 95; 96; 97], miR-92a may contribute to the deregulation of estrogen levels induced by shift work.