Chronic NR feeding increases NAD+ in vivo in a tissue-specific manner
We next wondered how chronic NR feeding would affect NAD+ metabolism in mice. Chronic NR supplementation increased NAD+ levels in both CD (Fig.S4A) and HFD (Fig.5A) conditions in some tissues, including liver and muscle, but not in others, such as brain or white adipose tissue (WAT). Interestingly, NAD+ was also higher in the BAT of NR-fed mice, but only on HFD (Fig.5B and Fig.S4A). These differences could be due to the differential expression of NRKs in tissues. NRKs initiate NR metabolism into NAD+ (Houtkooper et al., 2010). There are two mammalian NRKs: NRK1 and NRK2 (Bieganowski and Brenner, 2004). While we found NRK1 expressed ubiquitously (Fig.S4B), NRK2 was mainly present in cardiac and skeletal muscle tissues, as previously described (Li et al., 1999), but also detectable in BAT and liver (Fig.S4C), in line with the better ability of these tissues to respond to NR.