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<p>Hepatic nicotinamide adenine dinucleotide (NAD<sup>+</sup>) reduction is a pathological hallmark and pathogenic basis for alcohol-associated liver disease (ALD). This study investigated the therapeutic role of nicotinamide mononucleotide (NMN), a NAD<sup>+</sup> precursor naturally presenting in various dietary sources, against ALD. Here, we show that NMN supplementation attenuates NAD<sup>+</sup> decline, which in turn attenuates hepatic lipid deposition, dysregulated lipid metabolism genes, oxidative stress, and inflammation in ALD mice, and ultimately ameliorated liver injury. Transcriptomics-based mechanistic analysis demonstrates that alcohol-reduced hepcidin antimicrobial peptide (<i>Hamp</i>) is rescued by NMN, alongside the recovery of circulatory and hepatic iron levels. The hepatic <i>Hamp</i> expression is positively associated with NAD<sup>+</sup> content in the liver. <i>Hamp</i> knockdown significantly abolishes NMN-improved lipid accumulation and the dysregulation of lipid metabolism-related genes in ethanol-treated hepatocytes. Further analysis identifies a C/EBPα-involved transcriptional regulation mechanism in NMN-protected <i>Hamp</i> in ALD. These findings identify NMN as a promising dietary therapeutic for ALD, acting via the C/EBPα/<i>Hamp</i> signaling axis.</p><p></p>

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Hepatic Hamp restoration contributes to nicotinamide mononucleotide (NMN)-alleviated hepatic steatosis in chronic alcohol-fed mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月1日

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  • Feiwei Cao,
  • Xinxuan Ge,
  • Aiwen Pi,
  • Qingling Huang,
  • Liuhua Pei,
  • Rucheng Chen,
  • Wenjing Cao,
  • Qinchao Ding,
  • Min Yang,
  • Qing Song,
  • Hui Wang,
  • Songtao Li

摘要

Hepatic nicotinamide adenine dinucleotide (NAD+) reduction is a pathological hallmark and pathogenic basis for alcohol-associated liver disease (ALD). This study investigated the therapeutic role of nicotinamide mononucleotide (NMN), a NAD+ precursor naturally presenting in various dietary sources, against ALD. Here, we show that NMN supplementation attenuates NAD+ decline, which in turn attenuates hepatic lipid deposition, dysregulated lipid metabolism genes, oxidative stress, and inflammation in ALD mice, and ultimately ameliorated liver injury. Transcriptomics-based mechanistic analysis demonstrates that alcohol-reduced hepcidin antimicrobial peptide (Hamp) is rescued by NMN, alongside the recovery of circulatory and hepatic iron levels. The hepatic Hamp expression is positively associated with NAD+ content in the liver. Hamp knockdown significantly abolishes NMN-improved lipid accumulation and the dysregulation of lipid metabolism-related genes in ethanol-treated hepatocytes. Further analysis identifies a C/EBPα-involved transcriptional regulation mechanism in NMN-protected Hamp in ALD. These findings identify NMN as a promising dietary therapeutic for ALD, acting via the C/EBPα/Hamp signaling axis.