송원석 (University of California, Irvine) | 한빛사논문 > 한빛사

한빛사논문

조회262

University of California, Irvine

Cell Metab., May 01, 2025 | https://doi.org/10.1016/j.cmet.2025.04.007 Nicotinic acid riboside maintains NAD+ homeostasis and ameliorates aging-associated NAD+ decline

Won-Suk Song,^1,10 Xiyu Shen,^2,10 Kang Du,^2,10 Cuauhtemoc B. Ramirez,^1,3 Sang Hee Park,² Yang Cao,² Johnny Le,¹Hosung Bae,¹Joohwan Kim,³ Yujin Chun,³ Nikki Joyce Khong,¹ Marie Kim,¹ Sunhee Jung,¹ Wonsuk Choi,¹Miranda L. Lopez,¹ Zaid Said,² Zehan Song,⁵Sang-Guk Lee,^1,6 Dequina Nicholas,^1,4Yo Sasaki,⁷Jeffrey Milbrandt,⁷David K. Imagawa,⁸ Dorota Skowronska-Krawczyk,⁹ Danica Chen,⁵ Gina Lee,³ Cholsoon Jang,^1,* and Qin Yang ^2,11,*

¹Department of Biological Chemistry, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Irvine, CA 92697, USA
²Department of Medicine, Physiology and Biophysics, University of California, Irvine, School of Medicine, Irvine, CA 92697, USA
³Department of Microbiology and Molecular Genetics, Center for Epigenetics and Metabolism, Chao Family
Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Irvine, CA 92697, USA
⁴Department of Molecular Biology and Biochemistry, University of California, Irvine, School of Biological Sciences, Irvine, CA 92697, USA
⁵Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA
⁶Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, South Korea
⁷Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110, USA
⁸Division of Vascular and Endovascular Surgery, Department of Surgery, University of California, Irvine, Orange, CA 92868, USA
⁹Department of Physiology and Biophysics, Department of Ophthalmology, University of California, Irvine, School of Medicine, Irvine, CA 92697, USA
¹⁰These authors contributed equally
¹¹Lead contact

^*Corresponding authors: correspondence to Cholsoon Jang or Qin Yang

Abstract

Liver-derived circulating nicotinamide from nicotinamide adenine dinucleotide (NAD⁺) catabolism primarily feeds systemic organs for NAD⁺ synthesis. We surprisingly found that, despite blunted hepatic NAD⁺ and nicotinamide production in liver-specific nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) deletion mice (liver-specific knockout [LKO]), circulating nicotinamide and extra-hepatic organs’ NAD⁺ are unaffected. Metabolomics reveals a massive accumulation of a novel molecule in the LKO liver, which we identify as nicotinic acid riboside (NaR). We further demonstrate cytosolic 5′-nucleotidase II (NT5C2) as the NaR-producing enzyme. The liver releases NaR to the bloodstream, and kidneys take up NaR to synthesize NAD⁺ through nicotinamide riboside kinase 1 (NRK1) and replenish circulating nicotinamide. Serum NaR levels decline with aging, whereas oral NaR supplementation in aged mice boosts serum nicotinamide and multi-organ NAD⁺, including kidneys, and reduces kidney inflammation and albuminuria. Thus, the liver-kidney axis maintains systemic NAD⁺ homeostasis via circulating NaR, and NaR supplement ameliorates aging-associated NAD⁺ decline and kidney dysfunction.

논문정보

형식Research article
게재일2025년 05월 (BRIC 등록일 2025-05-02)
연구진국내+국외 연구진
분야 생명과학 > 생화학

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