Nicotinamide adenine dinucleotide (NAD⁺) is an essential metabolic co-factor that is central to energy metabolism. During aging, obesity, and diabetes, NAD⁺ concentrations in cells decline. NAD⁺ is synthesized de novo from tryptophan precursors, from nicotinic acid through the Preiss-Handler pathway, or from nicotinamide through the salvage pathway. The rate-limiting enzyme in the salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT), recycles nicotinamide into nicotinamide mononucleotide (NMN), which is converted into NAD⁺ (see the figure). Restoration of NAD⁺ concentrations in cells of old or diseased mice through administration of NMN improves health; however, it is unclear whether NMN therapy is practical in humans. On page 1224 of this issue, Yoshino et al. (1) show in a randomized, placebo-controlled, double-blind trial that NMN supplementation promotes NAD⁺ metabolism and improves skeletal muscle insulin sensitivity in postmenopausal prediabetic women who are overweight or obese. Thus, NMN may be a viable therapeutic strategy in humans to improve metabolic health during obesity.

烟酰胺腺嘌呤二核苷酸 (NAD ⁺ ) 是一种重要的代谢辅助因子，对能量代谢至关重要。在衰老、肥胖和糖尿病期间，细胞中的 NAD ⁺浓度会下降。NAD ⁺从色氨酸前体、烟酸通过 Preiss-Handler 途径从头合成，或从烟酰胺通过补救途径从头合成。补救途径中的限速酶烟酰胺磷酸核糖基转移酶 (NAMPT) 将烟酰胺再循环为烟酰胺单核苷酸 (NMN)，后者再转化为 NAD ⁺（见图）。^{NAD +}的恢复通过给予 NMN，老龄或患病小鼠细胞中的浓度可以改善健康；然而，尚不清楚 NMN 疗法是否适用于人类。在本期第 1224 页，Yoshino等人。( 1 ) 在一项随机、安慰剂对照、双盲试验中表明，补充 NMN 可促进超重或肥胖的绝经后糖尿病前期女性的NAD ^{+代谢并改善骨骼肌胰岛素敏感性。}因此，NMN 可能是人类改善肥胖期间代谢健康的可行治疗策略。