Cold-induced non-shivering thermogenesis (CIT) of the human body is currently discussed as an important contributor to energy metabolism, and miRNAs have recently been reported as key regulators of metabolism. Identifying the link of CIT and circulating microRNAs (miRNAs) in a large cohort of human individuals remains elusive to date. Here, we analyzed a set of 158 miRNAs in the serum of 97 female and 72 male healthy individuals before and after cold exposure (CE). Validating the results of a miRNA array, a significant down-regulation of miR-375 was measured in individuals after CIT (P<0.0001). These changes went along with a significant negative correlation between miR‑375 and the supraclavicular skin temperature (P=0.012).
Additionally, the regulation of miR-375 was sex-dependent, with female individuals showing a significantly stronger decrease in expression of miR-375 under CIT compared to males. Such findings were already seen under thermoneutral conditions, where females display significant lower miR-375 expression levels (P=0.015). Besides, the lower miR‑375 expression levels were negatively correlated with the amount of visceral fat tissue in the female cohort (P=0.0002).
This study identified miR-375 as a potential new sex-dependent marker for cold-induced thermogenesis.