# Exosomal miR-92a Concentration in the Serum of Shift Workers
## 1 Introduction  
Working on a shift work schedule implies that some daily habits, such as sleeping or eating, are not conducted with regular occurrence [1] resulting in a possible desynchronization between external and biological times [2]. The perturbation of the biological clock leads to alterations of several metabolic processes including reduced glucose tolerance, dislipydemia, weight gain [2; 3; 4], and the impairment of some molecules related to fat absorption and metabolism [2; 5]. Epidemiological studies associated shift work with an increased incidence of metabolic syndrome [6; 7] that, in turn, is an important cardiovascular risk factor [8; 9]. Since alterations of metabolic parameters and weight gain in shift workers do not seem to be associated with low physical activity or increased food intake [5; 10], it is likely that there are other factors that may influence energy balance.  
In the last few decades, brown adipose tissue (BAT) has regained scientific and public interest for its role in metabolism and weight gain [11; 12; 13; 14; 15; 16]. BAT is a rich vascularized tissue with a high number of mitochondria. It catabolizes lipids to generate heat playing a major role in thermogenesis and energy expenditure [17; 18; 19; 20]. Similar to lipids, BAT also metabolizes carbohydrates, contributing to the homeostasis of these two groups of macromolecules resulting in a beneficial effect on overall metabolism [21; 22; 23]. Obese patients have less active BAT [24]. In fact, an inverse relationship between active BAT and body mass index (BMI) has been discovered [25].  
The most used method for quantitatively measuring BAT volume and activity is the \({}^{18}\)fluor-deoxyglucose positron emission tomography coupled with computed tomography (FDG-PET/CT) [11]. Sincethis method is costly, labor-intensive, and involves exposure to radiation, some parameters were recently studied as biomarkers of BAT activity.  
MiRNAs are small, non-coding RNAs which regulate protein expression in several tissues [26; 27; 28]. MiRNAs are molecules that complementary bind mRNA and downregulate gene expression by translational repression, mRNA cleavage, and deadenylation [29]. MiRNAs are carried by exosomes, which are small lipid vesicles (40-100 nm in size) that constitute cell-to-cell communication [30; 31]. Exosomes allow an exchange of material between cells in an autocrine, paracrine, and even endocrine manner [32; 33]. MiRNAs present in human blood are stable and they are resistant to endogenous RNase activity [34]. MiRNAs are involved in the regulation of several pathological processes and represent new diagnostic and prognostic biomarkers for the diagnosis of various diseases [35]. Several miRNAs have proven to play a major role in BAT, such as controlling brown adipocytes differentiation [36]. Among these miRNAs, miR-92a has been involved in several metabolic processes, such as glucose homeostasis [24], regulation of intracellular cholesterol levels [37], and essential hypertension [38]. Furthermore, [PERSON] and collaborators demonstrated that serum levels of exosomal miR-92a were inversely correlated with human BAT activity, confirming the data by FDG-PET/CT [39]. Due to miR-92a in serum exosomes can easily be assessed, it could be considered a non-invasive biomarker for BAT activity [39].  
In light of this information, it was decided to study the levels of miR-92a in shift and daytime workers.