Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD+ metabolism in humans

Cold-induced brown adipose tissue (BAT) activation is considered to improve metabolic health. In murine BAT, cold increases the fundamental molecule for mitochondrial function, nicotinamide adenine dinucleotide (NAD+), but limited knowledge of NAD+ metabolism during cold in human BAT metabolism exists. We show that cold increases the serum metabolites of the NAD+ salvage pathway (nicotinamide and 1-methylnicotinamide) in humans. Additionally, individuals with cold-stimulated BAT activation have decreased levels of metabolites from the de novo NAD+ biosynthesis pathway (tryptophan, kynurenine). Serum nicotinamide correlates positively with cold-stimulated BAT activation, whereas tryptophan and kynurenine correlate negatively. Furthermore, the expression of genes involved in NAD+ biosynthesis in BAT is related to markers of metabolic health. Our data indicate that cold increases serum tryptophan conversion to nicotinamide to be further utilized by BAT. We conclude that NAD+ metabolism is activated upon cold in humans and is probably regulated in a coordinated fashion by several tissues. [Display omitted] •Cold induces a change in serum metabolites that are essential to NAD+ metabolism•Circulatory NAM, tryptophan, and kynurenine are linked to BAT activation during cold•NAD+ biosynthesis pathways are upregulated in BAT compared with WAT•BAT NAD+ biosynthesis is related to whole-body metabolic health U-Din et al. show that cold-stimulated BAT metabolism is linked to circulatory serum metabolites crucial for NAD+ biosynthesis. In BAT, the pathways of NAD+ biosynthesis, upregulated in comparison to WAT, are linked to thermogenic mechanisms and with whole-body metabolic health.