Functional involvement of Na<sup>+</sup>/Ca<sup>2+</sup> exchanger type 1 in brown adipose tissue thermogenesis

Brown adipose tissue (BAT) is a primary site for non-shivering thermogenesis in mammals. In cold temperature, β-adrenergic stimulation activates mitochondrial uncoupling protein 1 (UCP1), which consequently generates heat by uncouples of the respiratory chain. Previous report suggested that intracellular Ca2+ signaling induced by transient receptor potential vanilloid 2 (TRPV2) activates UCP1 in BAT thermogenesis. However, molecular mechanisms of intracellular Ca2+ signaling in BAT are not well characterized. We have been systematically studying the physiological functions of Na+/Ca2+ exchangers, which regulate intracellular Ca2+ signaling. Recently, we found that Na+/Ca2+ exchanger type 1 (NCX1) is abundantly expressed in interscapular BAT (iBAT) from wild-type mice. Therefore, in this study, our research interest focuses on elucidating functional involvement of NCX1 in BAT thermogenesis. Intriguingly, we observed that NCX1-heterozygous (NCX+/-) mice did not maintain their core body temperature in cold exposure. Furthermore, UCP1 transcripts in iBAT were significantly decreased in NCX+/- mice compared with wild-type mice. These results suggest that NCX1 may contribute to BAT thermogenesis against cold environment.