Arginase Activities and Global Arginine Bioavailability in Wild-Type and ApoE-Deficient Mice: Responses to High Fat and High Cholesterol Diets

PLoS One

Rebecca Salmen-Muniz¹  Tracy Hulderman²  Diane Kepka-Lenhart²  Sidney M. Morris Jr.²  Michael Kashon³  Aaron Erdely³  Rebecca Chapman³  Petia P. Simeonova³ 

[1] Biostatistics and Epidemiology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America;Laboratory for Occupational Cardiovascular Toxicology, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America;Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America

关键词: Diet;    Arginine;    Blood plasma;    Cholesterol;    Mouse models;    Trophic interactions;    Fats;    Amino acid metabolism;   

DOI  :  10.1371/journal.pone.0015253

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Increased catabolism of arginine by arginase is increasingly viewed as an important pathophysiological factor in cardiovascular disease, including atherosclerosis induced by high cholesterol diets. Whereas previous studies have focused primarily on effects of high cholesterol diets on arginase expression and arginine metabolism in specific blood vessels, there is no information regarding the impact of lipid diets on arginase activity or arginine bioavailability at a systemic level. We, therefore, evaluated the effects of high fat (HF) and high fat-high cholesterol (HC) diets on arginase activity in plasma and tissues and on global arginine bioavailability (defined as the ratio of plasma arginine to ornithine + citrulline) in apoE−/− and wild-type C57BL/6J mice. HC and HF diets led to reduced global arginine bioavailability in both strains. The HC diet resulted in significantly elevated plasma arginase in both strains, but the HF diet increased plasma arginase only in apoE−/− mice. Elevated plasma arginase activity correlated closely with increased alanine aminotransferase levels, indicating that liver damage was primarily responsible for elevated plasma arginase. The HC diet, which promotes atherogenesis, also resulted in increased arginase activity and expression of the type II isozyme of arginase in multiple tissues of apoE−/− mice only. These results raise the possibility that systemic changes in arginase activity and global arginine bioavailability may be contributing factors in the initiation and/or progression of cardiovascular disease.

【 授权许可】

CC BY