Nicotinamide Riboside Restores Mitochondrial Activity and Thermogenesis in Brown Fat: Preclinical Findings

Synopsis

Brown adipose tissue (BAT) depends on NAD+ biosynthesis for healthy mitochondrial function and thermogenesis. Multi-omics analysis of BXD mouse strains showed that BAT NAD+ metabolism strongly correlates with body weight, adiposity, insulin resistance, oxygen consumption, exercise capacity, and mitochondrial health. A high-fat diet (HFD) disrupted this pathway—lowering Nampt and NMNAT3, reducing NAD+ levels, inducing mitochondrial damage, and impairing BAT thermogenesis. Oral nicotinamide riboside (NR) supplementation restored NAD+ levels, preserved mitochondrial structure, prevented BAT whitening, and rescued thermogenic capacity in HFD-fed mice. These findings highlight NAD+ synthesis in BAT as a therapeutic target and position NR as a promising strategy to counteract obesity-related metabolic dysfunction.

Journal

The Journal of Physiology