Hepatoprotective Effect of Nicotinamide Mononucleotide on High‐Fat Diet‐Induced Non‐Alcoholic Fatty Liver Disease in Mice
- 1Institute of Clinical Anatomy and Reproductive Medicine, Department of Histology and Embryology, Hengyang Medical School University of South China Hengyang Hunan China.
- 2Youjiang District Ethnic Medicine College Baise City Guangxi Zhuang Autonomous Region China.
- 3Reproductive Hospital of Guangxi Zhuang Autonomous Region Nanning China.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a significant global public health issue characterized by hepatic lipid accumulation. Nicotinamide adenine dinucleotide (NAD+) is a crucial cofactor in cellular metabolism across mammalian organs. Nicotinamide mononucleotide (NMN), an important intermediate in NAD+ salvage synthesis, may influence high-fat diet (HFD)-induced hepatic steatosis. An HFD-induced NAFLD mouse model was established in C57BL/6 mice, followed by NMN administration for 8 weeks. HepG2 cells were treated with palmitic acid and co-incubated with NMN to establish an in vitro lipid accumulation model. Network pharmacology analysis and transcriptomic profiling were performed to identify potential molecular targets and pathways involved in the protective effects of NMN against NAFLD. Lipid accumulation was evaluated by H&E staining and Oil Red O staining. Serum lipid metabolism parameters were measured using assay kits. Quantitative RT-PCR and Western blotting were used to examine the expression of pathway-related genes and proteins to investigate the potential mechanism by which NMN alleviates hepatic steatosis. Compared with the HFD model group, NMN intervention significantly reduced body weight and alleviated hepatic steatosis. It also lowered levels of low-density lipoprotein (LDL), triglycerides, total cholesterol, and fasting blood glucose, while increasing high-density lipoprotein (HDL) levels. Liver PPAR-γ levels decreased, while HNF4α and SHBG levels increased. These findings suggest that the protective effects of NMN on HFD-induced hepatic steatosis are associated with decreased hepatic PPAR-γ expression and increased HNF4α and SHBG expression. NMN showed protective effects against HFD-induced NAFLD, which were associated with improvements in hepatic lipid metabolism. By integrating network pharmacology, transcriptomic analysis, and experimental validation, this study provides initial evidence regarding molecular changes associated with the effects of NMN in NAFLD.
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BibTeX
@article{zhang2026hepatoprotective,
title = {{Hepatoprotective Effect of Nicotinamide Mononucleotide on High‐Fat Diet‐Induced Non‐Alcoholic Fatty Liver Disease in Mice}},
author = {Yiwen Zhang and Yafei Wu and Yanhong Wei and Xuan Liu and Xiaocan Lei and Hua Huang and Meixiang Li},
journal = {Food science \& nutrition},
year = {2026},
month = oct,
doi = {10.1002/fsn3.72465},
url = {https://europepmc.org/article/PMC/PMC13717060},
note = {CC BY},
}
RIS
TY - JOUR
TI - Hepatoprotective Effect of Nicotinamide Mononucleotide on High‐Fat Diet‐Induced Non‐Alcoholic Fatty Liver Disease in Mice
AU - Yiwen Zhang
AU - Yafei Wu
AU - Yanhong Wei
AU - Xuan Liu
AU - Xiaocan Lei
AU - Hua Huang
AU - Meixiang Li
PY - 2026
DA - 2026/10/28
JO - Food science & nutrition
DO - 10.1002/fsn3.72465
UR - https://europepmc.org/article/PMC/PMC13717060
AB - Non-alcoholic fatty liver disease (NAFLD) is a significant global public health issue characterized by hepatic lipid accumulation. Nicotinamide adenine dinucleotide (NAD+) is a crucial cofactor in cellular metabolism across mammalian organs. Nicotinamide mononucleotide (NMN), an important intermediate in NAD+ salvage synthesis, may influence high-fat diet (HFD)-induced hepatic steatosis. An HFD-induced NAFLD mouse model was established in C57BL/6 mice, followed by NMN administration for 8 weeks. HepG2 cells were treated with palmitic acid and co-incubated with NMN to establish an in vitro lipid accumulation model. Network pharmacology analysis and transcriptomic profiling were performed to identify potential molecular targets and pathways involved in the protective effects of NMN against NAFLD. Lipid accumulation was evaluated by H&E staining and Oil Red O staining. Serum lipid metabolism parameters were measured using assay kits. Quantitative RT-PCR and Western blotting were used to examine the expression of pathway-related genes and proteins to investigate the potential mechanism by which NMN alleviates hepatic steatosis. Compared with the HFD model group, NMN intervention significantly reduced body weight and alleviated hepatic steatosis. It also lowered levels of low-density lipoprotein (LDL), triglycerides, total cholesterol, and fasting blood glucose, while increasing high-density lipoprotein (HDL) levels. Liver PPAR-γ levels decreased, while HNF4α and SHBG levels increased. These findings suggest that the protective effects of NMN on HFD-induced hepatic steatosis are associated with decreased hepatic PPAR-γ expression and increased HNF4α and SHBG expression. NMN showed protective effects against HFD-induced NAFLD, which were associated with improvements in hepatic lipid metabolism. By integrating network pharmacology, transcriptomic analysis, and experimental validation, this study provides initial evidence regarding molecular changes associated with the effects of NMN in NAFLD.
SN - 2048-7177
ER -