2. Academic Validation
  3. Nicotinamide mononucleotide treatment improves spermatogenesis in obese mice by reducing lysine acetylation of lactate dehydrogenase C

Nicotinamide mononucleotide treatment improves spermatogenesis in obese mice by reducing lysine acetylation of lactate dehydrogenase C

  • Commun Biol. 2025 Nov 26;8(1):1761. doi: 10.1038/s42003-025-09094-5.
Ke Liu # 1,  Weihua Nong # 2,  Hua Huang # 3,  Yanhong Wei 2,  Jinyuan Wang 4,  Li Youzhu 5 6,  Guoqing Huang 1,  Zhanyou Tang 1,  Jingjing Yu 7,  Peng Huo 7,  Linlin Hu 2,  Xi Chen 1,  Xiangdong Wang 8,  Xiaocan Lei 9
Affiliations

Affiliations

  • 1 University of South China-Hengyang Maternal and Child Health Hospital Joint Training Base for Top Innovative Graduate Talents, College of Basic Medical Sciences, Hengyang Medical School, Hengyang, China.
  • 2 Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Department of Obstetrics and Gynecology, Department of Reproductive Medicine Center, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
  • 3 Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi, China.
  • 4 Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
  • 5 Department of Reproductive Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
  • 6 College of Animal Science and Technology, China Agricultural University, Beijing, China.
  • 7 School of Public Health, Guilin Medical University, Guilin, China.
  • 8 University of South China-Hengyang Maternal and Child Health Hospital Joint Training Base for Top Innovative Graduate Talents, College of Basic Medical Sciences, Hengyang Medical School, Hengyang, China. [email protected].
  • 9 University of South China-Hengyang Maternal and Child Health Hospital Joint Training Base for Top Innovative Graduate Talents, College of Basic Medical Sciences, Hengyang Medical School, Hengyang, China. [email protected].
  • # Contributed equally.
PMID: 41298813 DOI: 10.1038/s42003-025-09094-5
Abstract

Obesity is associated with impaired spermatogenesis and decreased sperm quality, in part through reducing Sertoli cells (SCs) lactate and nicotinamide adenine dinucleotide (NAD+) production. It is not known whether nicotinamide mononucleotide (NMN) treatment improves spermatogenesis. In the present study, NMN improved lipid metabolism and enhanced spermatogenesis in obese mice, alleviated SCs dysfunction in vivo and in vitro. Label-free quantitative acetylomics analysis of mouse testes suggested that protein acetylation influenced both the structural and functional properties of metabolic proteins. The beneficial effects of NMN were due in part to changes in the acetylation of glycolysis-related proteins. Furthermore, multi-omics and correlation analyses demonstrated that interactions among the gut microbiota, metabolites, spermatogenesis, and LDHC acetylation mediated the beneficial effects of NMN. Importantly, we found that NMN treatment reduced acetylation of the lysine residues 5, 17, and 90 of LDHC, which plays a critical role in SC lactate production in obesity. Collectively, our findings show that NMN supplementation improves sperm quality in obese mice by decreasing LDHC acetylation, thereby increasing Sertoli cell lactate and NAD+ production.

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