Circulating miR-375 Correlates With Response of Human Individuals to Short-Term Cold Exposure

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.

The Supraclavicular Skin Temperature Response to Mild Cold Stimulation is Dependent on Ambient Temperature

Purpose: This study investigated the basal activity, and cold-induced thermogenic response, of supraclavicular brown adipose tissue (BAT) under warm (23˚C) and cool (18˚C) ambient conditions using supraclavicular skin temperature as a measure of BAT activity. As a highly metabolic, heat-producing tissue, it has been hypothesised that under-active/dysfunctional BAT may underlie a pathological energy imbalance leading to obesity. Methods: Five lean, healthy participants underwent infrared thermography (IRT) of supraclavicular BAT before, and during, mild cold exposure (single-hand immersion in cool water at 20˚C), once at 18˚C and once at 23˚C. Energy expenditure (EE) was measured simultaneously using indirect calorimetry, and mean skin temperature (TMSK) was calculated at 1-minute intervals in parallel to IRT using wireless data loggers. Results: Following 30 minutes of hand cooling, supraclavicular skin temperature (TSCR) rose significantly from baseline at an ambient temperature of 23˚C (∆TSCR: 0.17 ± 0.03˚C, P < 0.01), and EE rose by 0.22 ± 0.02 kJ/min, P < 0.001. At an ambient room temperature of 18˚C, TSCR after hand cooling was similar to baseline, and EE remained unchanged. The TMSK response was indicative of a systemic vasoconstrictive response of similar magnitude in both warm and cool ambient temperatures. Conclusions: At 18˚C in light clothing, BAT may already be maximally stimulated at baseline, and respond minimally to additional cold exposure. Ambient temperature is recognised as a determinant of glucose uptake in BAT. In this study, we show, that it also modulates the TSCR response to further localised cold-stimulation, indicating an effect on BAT thermogenesis.