Raúl Pérez Mato

White adipose tissue (WAT) stores energy, whereas brown AT (BAT) is specialized in energy expenditure. WAT browning has been suggested as a strategy in obesity, insulin resistance and T2D, but the browning-inducing methods identified so far are not appropriate as therapies: mechanisms to induce long-lasting WAT browning are highly demanded. NAD(P)⁺ are crucial in mitochondrial oxidative and lipid metabolism. NAD⁺ tissue levels decrease upon aging/obesity and approaches to boost NAD are tested to promote healthy aging and metabolism. Cold-exposed cd38-/- mice had higher levels of browning markers in BAT/WAT and this effect was attributed to NAD increase. A marked downregulation of CD38 expression in BAT/WAT from cold-exposed wild-type mice, was also unveiled, determining the increase of NAD⁺ in BAT, and of NADP(H) in WAT. Expression/activities of NADK and G6PD producing NADP/NADPH were enhanced in WAT, but the mechanisms linking these activities to NAD⁺ levels are not clarified. Thus, I will investigate: (1) the mechanism for the beneficial effect of CD38 downregulation in browning, (2) the mechanisms upregulating NADK and G6PD expression/activity during browning