Obesity-induced vascular inflammation involves elevated arginase activity

Lin Yao, Anil Bhatta, Zhimin Xu, Jijun Chen, Haroldo A. Toque, Yongjun Chen, Yimin Xu, Zsolt Bagi, Rudolf Lucas, Yuqing Huo, Ruth B. Caldwell, R. William Caldwell

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Obesity- induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC-A1 activity also drives obesityrelated VAT remodeling and inflammation. Our studies utilized wildtype and EC-A1 knockout (KO) mice made obese by high-fat/highsucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule- 1 (ICAM-1) mRNA and protein in both VAT and ECs. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-(S)- amino-6-boronohexanoic acid (ABH). In mouse aortic ECs, exposure to high glucose (25 mM) and Na palmitate (200 µM) reduced nitric oxide production and increased A1, TNF-α, VCAM-1, ICAM-1, and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. HFHS diet-induced VAT inflammation is mediated by EC-A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation.

Original languageEnglish (US)
Pages (from-to)R560-R571
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume313
Issue number5
DOIs
StatePublished - Nov 2017

Keywords

  • Arginase
  • Endothelial cell activation
  • Inflammation
  • Macrophage
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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