Obesity-induced vascular inflammation involves elevated arginase activity.

Area of Science:

• Vascular Biology
• Metabolic Syndrome
• Adipose Tissue Biology

Background:

• Obesity leads to vascular dysfunction and visceral adipose tissue (VAT) inflammation.
• Endothelial cell arginase 1 (A1) is implicated in obesity-induced vascular dysfunction.

Purpose of the Study:

• To investigate the role of endothelial cell arginase 1 (A1) in obesity-related VAT remodeling and inflammation.
• To determine if targeting A1 activity can mitigate obesity-induced vascular and VAT inflammation.

Main Methods:

• Utilized wild-type and EC-A1 knockout mice fed a high-fat/high-sucrose (HFHS) diet.
• Assessed metabolic parameters, VAT expansion, inflammation markers (TNF-α, MCP-1, IL-10, VCAM-1, ICAM-1), macrophage infiltration, adipocyte size, fibrosis, and capillary density.
• Treated mice with the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH).
• Examined effects of high glucose and palmitate on mouse aortic endothelial cells (ECs) in vitro.

Main Results:

• HFHS diet increased body weight, glucose, VAT expansion, and inflammation in wild-type mice.
• EC-A1 knockout or ABH treatment prevented or reduced HFHS-induced VAT inflammation and remodeling, except for weight gain and hyperglycemia.
• In vitro, high glucose and palmitate increased A1 expression and inflammatory markers in ECs, which was prevented by EC-A1 knockout or ABH.
• HFHS diet increased inflammatory monocytes and VAT macrophages, while decreasing reparative macrophages, effects mitigated by EC-A1 deficiency.

Conclusions:

• Endothelial cell arginase 1 (A1) activity is a key mediator of obesity-induced VAT inflammation and pathological remodeling.
• Limiting arginase activity presents a potential therapeutic strategy for managing obesity-related vascular and VAT inflammation.