Nicotinamide riboside enhances in vitro beta-adrenergic brown adipose tissue activity in humans.

Context Elevating NAD+ levels systemically improves metabolic health, which can be accomplished via nicotinamide riboside (NR). Previously, it was demonstrated that NR supplementation in high fat diet (HFD)-fed mice decreased weight gain, normalized glucose metabolism and enhanced cold tolerance. Objective As brown adipose tissue (BAT) is a major source of thermogenesis, we hypothesize that NR stimulates BAT in mice and humans. Design and intervention HFD-fed C56BL/6J mice were supplemented with 400 mg/kg/day NR for 4 weeks and subsequently exposed to cold. In vitro primary adipocytes derived from human BAT biopsies were pretreated with 50 µM or 500 µM NR prior to measuring mitochondrial uncoupling. Human volunteers (45-65 years, BMI: 27-35 kg/m 2) were supplemented with 1000 mg/day NR for 6 weeks to determine whether BAT activity increased, as measured by [18F]FDG uptake via PET-CT (randomized, double blinded, placebo-controlled, cross-over study with NR supplementation). Results NR supplementation in HFD-fed mice decreased adipocyte cell size in BAT. Cold exposure further decreased adipocyte cell size on top of that achieved by NR alone independent of ex vivo lipolysis. In adipocytes derived from human BAT, NR enhanced in vitro norepinephrine-stimulated mitochondrial uncoupling. However, NR supplementation in human volunteers did not alter BAT activity or cold induced thermogenesis. Conclusions NR stimulates in vitro human BAT, however not in vivo BAT in humans. Our research demonstrates the need for further translational research to better understand the differences in NAD + metabolism in mouse and human.