Yoshino Mihoko, Yoshino Jun, Kayser Brandon D, Patti Gary J, Franczyk Michael P, Mills Kathryn F, Sindelar Miriam, Pietka Terri, Patterson Bruce W, Imai Shin-Ichiro, Klein Samuel
Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA.
Department of Chemistry, Washington University School of Medicine, St. Louis, MO, USA.
Science. 2021 Jun 11;372(6547):1224-1229. doi: 10.1126/science.abe9985. Epub 2021 Apr 22.
In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239).
在啮齿动物中，肥胖和衰老会损害烟酰胺腺嘌呤二核苷酸（NAD）的生物合成，这会导致代谢功能障碍。烟酰胺单核苷酸（NMN）的可利用性是哺乳动物NAD生物合成中的一个限速因素。我们进行了一项为期10周的随机、安慰剂对照、双盲试验，以评估补充NMN对超重或肥胖的糖尿病前期绝经后女性代谢功能的影响。通过高胰岛素-正常血糖钳夹评估的胰岛素刺激的葡萄糖处置以及骨骼肌胰岛素信号传导[蛋白激酶AKT和雷帕霉素机制靶点（mTOR）的磷酸化]在补充NMN后增加，但在安慰剂治疗后没有变化。补充NMN上调了血小板衍生生长因子受体β和其他与肌肉重塑相关基因的表达。这些结果表明，NMN可提高超重或肥胖的糖尿病前期女性的肌肉胰岛素敏感性、胰岛素信号传导和重塑（临床试验.gov NCT03151239）。
