Nicotinamide riboside enhances liver regeneration via the MCART1/ASB3 axis in obesity-compromised rats

Sep 29, 2026

Obesity impairs liver regeneration by driving chronic inflammation and metabolic dysfunction, reducing the effectiveness of portal vein embolization (PVE) used to stimulate growth before hepatectomy. Nicotinamide riboside (NR), a NAD+ precursor, improves mitochondrial function and lipid metabolism, but its mechanism in obese settings remains unclear. This study evaluates NR’s effects after PVE in high-fat diet–induced obese rats, using histology, EdU, immunohistochemistry, liver function tests, and mechanistic pathway analyses focused on the MCART1/ASB3 axis.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

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Abstract

Introduction

Methods

Results

Conclusions

DOI: 10.1097/HC9.0000000000000866 O R IG INAL ART ICL E Nicotinamide riboside enhances liver regeneration via the MCART1/ASB3 axis in obesity-compromised rats Hongbo Wang | Hai Li | Yang Liu | Xiangdong Wang | Chengjian He | Jian Huang | Yijun Zhang | Yefa Yang | Naijian Ge Mini-Invasive Intervention Center, Third Affiliated Hospital of Naval Medical University/ Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China Correspondence Naijian Ge, Mini-Invasive Intervention Center, Third Affiliated Hospital of Naval Medical University, No. 700, Moyu North Road, Jiading District, Shanghai 200438, China Email: [gelarge@smmu.edu.cn](gelarge@smmu.edu.cn) | | Abstract | | | --- | --- | --- | | | Background: Obesity impairs liver regeneration by promoting chronic inflammation and metabolic dysfunction, especially in conditions like nonalcoholic fatty liver disease. Portal vein embolization (PVE), used to stimulate liver growth pre-hepatectomy, is less effective in obese subjects. Nicotinamide riboside (NR), a NAD+ precursor, improves mitochondrial function and lipid metabolism, but its role in liver regeneration under obese conditions remains unclear. Our study tried to investigate the effects and underlying mechanisms of NR on liver regeneration after PVE in high-fat diet (HFD)-induced obese rats.
Methods: HFD-fed rats underwent PVE and were treated with or without NR. Liver regeneration was assessed by histology, 5-ethynyl-2′-deoxyuridine (EdU) incorporation, immunohistochemistry, and liver function tests. NAD+ levels were quantified to confirm NR activity. Proteomics, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Ontology (GO) analysis, quantitative real-time PCR (qPCR), and western blotting were used to explore molecular mechanisms, focusing on the MCART1/ASB3 axis.
Results: Obesity impaired liver regeneration post-PVE, as evidenced by lipid accumulation, inflammation, reduced hepatocyte proliferation, and elevated liver enzymes. NR supplementation restored NAD+ levels, improved liver function, increased proliferative activity, and reduced steatosis. Mechanistically, NR upregulated MCART1 and ASB3 expression, promoting energy and lipid metabolism essential for regeneration. | | | | | | Abbreviations: ALB, albumin; ALT, alanine aminotransferase; ANOVA, analysis of variance; ASB3, Ankyrin repeat and SOCS box containing 3 (lipid metabolism– related protein); AST, aspartate aminotransferase; BCA, bicinchoninic acid; cDNA, complementary DNA; DAB, 3,3’-Diaminobenzidine; DBIL, direct bilirubin; ECL, enhanced chemiluminescence; EdU, 5-ethynyl-2′-deoxyuridine (proliferation marker); GO, Gene Ontology; H&E, hematoxylin and eosin; HFD, high-fat diet; HRP, horseradish peroxidase; IgG, immunoglobulin G; IHC, immunohistochemistry; IL-1, interleukin-1; IL-6, interleukin-6; KEGG, Kyoto Encyclopedia of Genes and Genomes; MCART1, mitochondrial carrier triple repeat 1 (energy metabolism protein); NAD+, nicotinamide adenine dinucleotide; NAFLD, non-alcoholic fatty liver disease; NBCA, N-butyl cyanoacrylate (embolizing agent); NLRP3, NLR family pyrin domain containing 3 (inflammasome); NR, nicotinamide riboside; OCT, optimal cutting temperature; PBS, phosphate-buffered saline; PCA, principal component analysis; PVDF, polyvinylidene difluoride; PVE, portal vein embolization; qRT-PCR, quantitative real-time polymerase chain reaction; SD, Sprague–Dawley (rat strain); SDS–PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis; SIRT1/3, Sirtuin 1/3 (NAD+-dependent deacetylases); TBIL, total bilirubin; TNF-α, tumor necrosis factor-alpha; WB, western blotting. -- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- - This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work

FAQs

How does obesity affect liver regeneration after portal vein embolization (PVE)?

Obesity impairs liver regeneration post-PVE by increasing lipid accumulation and inflammation, reducing hepatocyte proliferation, and elevating liver enzymes.

What treatment was compared in the study of obese rats after PVE?

High-fat diet (HFD) rats underwent PVE and were treated with NR or without NR to assess effects on regeneration and underlying mechanisms.

What mechanism links NR to improved liver regeneration?

NR restores NAD+ levels and upregulates MCART1 and ASB3 expression, promoting energy and lipid metabolism pathways needed for regeneration.

Sep 29, 2026

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