Related Experiment Video
Updated: Apr 26, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
Arginase inhibition ameliorates hepatic metabolic abnormalities in obese mice
Jiyoung Moon1, Hyun Ju Do2, Yoonsu Cho1
1Department of Food and Nutrition, Korea University, Seoul, Republic of Korea; Department of Public Health Sciences, Graduate School, Korea University, Seoul, Republic of Korea.
Objectives:
We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity.
Methods And Results:
After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visceral fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in lipid metabolism. Expression of phosphorylated 5' AMPK-activated protein kinase α was increased by arginase inhibition in the mouse livers and HepG2 cells.
Conclusions:
Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function.
Insights
Arginase inhibition reduced obesity and liver fat in mice by increasing nitric oxide (NO) and activating key metabolic pathways. This suggests a potential therapeutic target for metabolic disorders.
Area of Science:
- Metabolic pathways
- Obesity research
- Pharmacology
Background:
- Diet-induced obesity is linked to hepatic lipid abnormalities and increased adiposity.
- Arginase plays a role in metabolic regulation, but its specific influence on obesity-related hepatic pathways is not fully understood.
Purpose of the Study:
- To investigate the effects of arginase inhibition on hepatic metabolic pathways and whole-body adiposity in a diet-induced obesity model.
- To determine if blocking arginase activity can ameliorate obesity-related metabolic dysfunction.
Main Methods:
- Mice were fed a high-fat diet (HFD) to induce obesity.
- Obese mice received either the HFD or HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA).
- In vitro studies used oleic acid-induced hepatic steatosis in HepG2 cells.
Main Results:
- Nor-NOHA treatment prevented increases in body, liver, and visceral fat weight, and improved lipid profiles in HFD-fed mice.
- Arginase inhibition reduced lipid accumulation in hepatic steatosis models and increased hepatic nitric oxide (NO) production.
- Treatment reversed elevated mRNA expression of hepatic genes involved in lipid metabolism and increased phosphorylated 5' AMP-activated protein kinase α (AMPKα).
Conclusions:
- Arginase inhibition effectively ameliorated obesity-induced hepatic lipid abnormalities and whole-body adiposity.
- These benefits are likely mediated by increased hepatic NO production, activating metabolic pathways crucial for triglyceride metabolism and mitochondrial function.
- Arginase inhibition presents a potential therapeutic strategy for managing obesity and associated metabolic disorders.
