Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice
Visceral adipose tissue (VAT) inflammation and metabolic dysregulation are key components of obesity-induced metabolic disease. Upregulated arginase, a ureahydrolase enzyme with two isoforms (A1-cytosolic and A2-mitochondrial), is implicated in pathologies associated with obesity and diabetes. This...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-03-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/20/6/1462 |
id |
doaj-42fae6d3be5f45f883299e981c191e10 |
---|---|
record_format |
Article |
spelling |
doaj-42fae6d3be5f45f883299e981c191e102020-11-25T01:56:26ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-03-01206146210.3390/ijms20061462ijms20061462Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese MiceReem T. Atawia0Haroldo A. Toque1Mohamed M. Meghil2Tyler W. Benson3Nicole K. H. Yiew4Christopher W. Cutler5Neal L. Weintraub6Ruth B. Caldwell7Robert W. Caldwell8Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USADepartment of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USADepartment of Periodontics, Dental College of Georgia, Augusta University, Augusta, GA 30912, USAVascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USADepartment of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USADepartment of Periodontics, Dental College of Georgia, Augusta University, Augusta, GA 30912, USAVascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USAVascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USADepartment of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USAVisceral adipose tissue (VAT) inflammation and metabolic dysregulation are key components of obesity-induced metabolic disease. Upregulated arginase, a ureahydrolase enzyme with two isoforms (A1-cytosolic and A2-mitochondrial), is implicated in pathologies associated with obesity and diabetes. This study examined A2 involvement in obesity-associated metabolic and vascular disorders. WT and globally deleted A2(<sup>−/−</sup>) or A1(<sup>+/−</sup>) mice were fed either a high fat/high sucrose (HFHS) diet or normal diet (ND) for 16 weeks. Increases in body and VAT weight of HFHS-fed WT mice were abrogated in A2<sup>−/−</sup>, but not A1<sup>+/−</sup>, mice. Additionally, A2<sup>−/−</sup> HFHS-fed mice exhibited higher energy expenditure, lower blood glucose, and insulin levels compared to WT HFHS mice. VAT and adipocytes from WT HFHS fed mice showed greater A2 expression and adipocyte size and reduced expression of <i>PGC-1α, PPAR-γ,</i> and adiponectin. A2 deletion blunted these effects, increased levels of active <i>AMPK-α</i>, and upregulated genes involved in fatty acid metabolism. A2 deletion prevented HFHS-induced VAT collagen deposition and inflammation, which are involved in adipocyte metabolic dysfunction. Endothelium-dependent vasorelaxation, impaired by HFHS diet, was significantly preserved in A2<sup>−/−</sup> mice, but more prominently maintained in A1<sup>+/−</sup> mice. In summary, A2 is critically involved in HFHS-induced VAT inflammation and metabolic dysfunction.https://www.mdpi.com/1422-0067/20/6/1462arginaseobesityinflammationmetabolismendothelial dysfunctionfatty acid oxidationAMPK-α |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Reem T. Atawia Haroldo A. Toque Mohamed M. Meghil Tyler W. Benson Nicole K. H. Yiew Christopher W. Cutler Neal L. Weintraub Ruth B. Caldwell Robert W. Caldwell |
spellingShingle |
Reem T. Atawia Haroldo A. Toque Mohamed M. Meghil Tyler W. Benson Nicole K. H. Yiew Christopher W. Cutler Neal L. Weintraub Ruth B. Caldwell Robert W. Caldwell Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice International Journal of Molecular Sciences arginase obesity inflammation metabolism endothelial dysfunction fatty acid oxidation AMPK-α |
author_facet |
Reem T. Atawia Haroldo A. Toque Mohamed M. Meghil Tyler W. Benson Nicole K. H. Yiew Christopher W. Cutler Neal L. Weintraub Ruth B. Caldwell Robert W. Caldwell |
author_sort |
Reem T. Atawia |
title |
Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice |
title_short |
Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice |
title_full |
Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice |
title_fullStr |
Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice |
title_full_unstemmed |
Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice |
title_sort |
role of arginase 2 in systemic metabolic activity and adipose tissue fatty acid metabolism in diet-induced obese mice |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-03-01 |
description |
Visceral adipose tissue (VAT) inflammation and metabolic dysregulation are key components of obesity-induced metabolic disease. Upregulated arginase, a ureahydrolase enzyme with two isoforms (A1-cytosolic and A2-mitochondrial), is implicated in pathologies associated with obesity and diabetes. This study examined A2 involvement in obesity-associated metabolic and vascular disorders. WT and globally deleted A2(<sup>−/−</sup>) or A1(<sup>+/−</sup>) mice were fed either a high fat/high sucrose (HFHS) diet or normal diet (ND) for 16 weeks. Increases in body and VAT weight of HFHS-fed WT mice were abrogated in A2<sup>−/−</sup>, but not A1<sup>+/−</sup>, mice. Additionally, A2<sup>−/−</sup> HFHS-fed mice exhibited higher energy expenditure, lower blood glucose, and insulin levels compared to WT HFHS mice. VAT and adipocytes from WT HFHS fed mice showed greater A2 expression and adipocyte size and reduced expression of <i>PGC-1α, PPAR-γ,</i> and adiponectin. A2 deletion blunted these effects, increased levels of active <i>AMPK-α</i>, and upregulated genes involved in fatty acid metabolism. A2 deletion prevented HFHS-induced VAT collagen deposition and inflammation, which are involved in adipocyte metabolic dysfunction. Endothelium-dependent vasorelaxation, impaired by HFHS diet, was significantly preserved in A2<sup>−/−</sup> mice, but more prominently maintained in A1<sup>+/−</sup> mice. In summary, A2 is critically involved in HFHS-induced VAT inflammation and metabolic dysfunction. |
topic |
arginase obesity inflammation metabolism endothelial dysfunction fatty acid oxidation AMPK-α |
url |
https://www.mdpi.com/1422-0067/20/6/1462 |
work_keys_str_mv |
AT reemtatawia roleofarginase2insystemicmetabolicactivityandadiposetissuefattyacidmetabolismindietinducedobesemice AT haroldoatoque roleofarginase2insystemicmetabolicactivityandadiposetissuefattyacidmetabolismindietinducedobesemice AT mohamedmmeghil roleofarginase2insystemicmetabolicactivityandadiposetissuefattyacidmetabolismindietinducedobesemice AT tylerwbenson roleofarginase2insystemicmetabolicactivityandadiposetissuefattyacidmetabolismindietinducedobesemice AT nicolekhyiew roleofarginase2insystemicmetabolicactivityandadiposetissuefattyacidmetabolismindietinducedobesemice AT christopherwcutler roleofarginase2insystemicmetabolicactivityandadiposetissuefattyacidmetabolismindietinducedobesemice AT neallweintraub roleofarginase2insystemicmetabolicactivityandadiposetissuefattyacidmetabolismindietinducedobesemice AT ruthbcaldwell roleofarginase2insystemicmetabolicactivityandadiposetissuefattyacidmetabolismindietinducedobesemice AT robertwcaldwell roleofarginase2insystemicmetabolicactivityandadiposetissuefattyacidmetabolismindietinducedobesemice |
_version_ |
1724980193186021376 |