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Significance Thermogenesis is a fundamental aspect of energy homeostasis. Here, we present evidence that adipose tissue NAD+ metabolism is essential for thermogenesis. We found cold exposure activates NAD+ biosynthesis mediated by a rate-limiting enzyme, NAMPT, in mouse and human brown adipose tissue (BAT). Loss of NAMPT impairs the gene programs involved in thermogenesis and mitochondrial function in BAT. Mice lacking NAMPT in both BAT and white adipose tissue (WAT) but not in BAT alone have impaired thermogenic responses to cold exposure, fasting, and β-adrenergic stimulation. In WAT, NAMPT deletion decreases adrenergic-mediated lipolysis through inactivation of caveolin-1, which likely impairs whole-body thermogenesis. Nicotinamide mononucleotide administration normalized these metabolic derangements. These findings demonstrate the importance of adipose tissue NAD+ biology in energy metabolism.

Adipose tissue NAD + biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice

Adipose tissue NAD ⁺ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice