Related Experiment Video
Updated: Apr 6, 2026
Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
Published on: March 17, 2023
Arginase inhibition ameliorates adipose tissue inflammation in mice with diet-induced obesity
Huan Hu1, Jiyoung Moon2, Ji Hyung Chung3
1Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul 136-701, Republic of Korea.
Abstract:
This study examined whether oral administration of an arginase inhibitor regulates adipose tissue macrophage infiltration and inflammation in mice with high fat diet (HFD)-induced obesity. Male C57BL/6 mice (n = 30) were randomly assigned to control (CTL, n = 10), HFD only (n = 10), and HFD with arginase inhibitor N(ω)-hydroxy-nor-l-arginine (HFD with nor-NOHA, n = 10) groups. Plasma and mRNA levels of cytokines in epididymal adipose tissues (EAT), macrophage infiltration into EAT, and macrophage phenotype polarization were measured in the animals after 12 weeks. Additionally, the effects of nor-NOHA on adipose tissue macrophage infiltration and mRNA expression of cytokines were measured in co-cultured 3T3-L1 adipocytes and RAW 264.7 macrophages. Macrophage infiltration into the adipocytes was significantly suppressed by nor-NOHA treatment in adipocyte/macrophage co-culture system and mice with HFD-induced obesity. Pro-inflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), were significantly downregulated, and the anti-inflammatory cytokine IL-10 was significantly upregulated in nor-NOHA-treated co-cultured cells. In the mice with HFD-induced obesity, plasma and mRNA levels of MCP-1 significantly reduced after supplementation with nor-NOHA. In addition, oral supplement of nor-NOHA modified M1/M2 phenotype ratio in the EAT. Oral supplementation of an arginase inhibitor, nor-NOHA, altered M1/M2 macrophage phenotype and macrophage infiltration into HFD-induced obese adipose tissue, thereby improved adipose tissue inflammatory response. These results may indicate that arginase inhibition ameliorates obesity-induced adipose tissue inflammation.
Insights
Arginase inhibition with nor-NOHA reduced macrophage infiltration and inflammation in obese mice. This treatment improved adipose tissue inflammatory responses by altering macrophage phenotypes and decreasing pro-inflammatory cytokines.
Area of Science:
- Immunology
- Metabolic Disease Research
- Pharmacology
Background:
- Obesity-induced adipose tissue inflammation is linked to macrophage infiltration and pro-inflammatory cytokine production.
- Arginase plays a role in macrophage function and inflammation, making it a potential therapeutic target.
Purpose of the Study:
- To investigate the effect of oral arginase inhibitor N(ω)-hydroxy-nor-l-arginine (nor-NOHA) on adipose tissue macrophage infiltration and inflammation in high-fat diet (HFD)-induced obesity.
- To determine if nor-NOHA modulates macrophage phenotype polarization and cytokine expression in obese mice and in vitro models.
Main Methods:
- Male C57BL/6 mice were fed a control, HFD, or HFD with nor-NOHA for 12 weeks.
- Macrophage infiltration, cytokine levels (MCP-1, TNF-α, IL-6, IL-10), and M1/M2 phenotype ratios in epididymal adipose tissue (EAT) were assessed.
- In vitro studies used co-cultures of 3T3-L1 adipocytes and RAW 264.7 macrophages treated with nor-NOHA.
Main Results:
- Nor-NOHA significantly suppressed macrophage infiltration into adipose tissue in both mice and the in vitro co-culture system.
- Pro-inflammatory cytokines (MCP-1, TNF-α, IL-6) were downregulated, while anti-inflammatory IL-10 was upregulated in nor-NOHA-treated groups.
- Oral nor-NOHA administration altered the M1/M2 macrophage phenotype ratio in the EAT of obese mice.
Conclusions:
- Oral administration of the arginase inhibitor nor-NOHA ameliorates obesity-induced adipose tissue inflammation.
- Arginase inhibition effectively reduces macrophage infiltration and modulates macrophage polarization, improving the inflammatory profile of adipose tissue.
