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Int. J. Mol. Sci. 2019, 20(6), 1462; https://doi.org/10.3390/ijms20061462

Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice

1
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USA
2
Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA
3
Department of Periodontics, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA
4
Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA
5
Current address: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
6
Charlie Norwood VA Medical Center, Augusta, GA 30904, USA
*
Author to whom correspondence should be addressed.
Received: 13 February 2019 / Revised: 14 March 2019 / Accepted: 19 March 2019 / Published: 22 March 2019
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue 2.0)
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Abstract

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(−/−) or A1(+/−) 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−/−, but not A1+/−, mice. Additionally, A2−/− 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 PGC-1α, PPAR-γ, and adiponectin. A2 deletion blunted these effects, increased levels of active AMPK-α, 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−/− mice, but more prominently maintained in A1+/− mice. In summary, A2 is critically involved in HFHS-induced VAT inflammation and metabolic dysfunction. View Full-Text
Keywords: arginase; obesity; inflammation; metabolism; endothelial dysfunction; fatty acid oxidation; AMPK-α arginase; obesity; inflammation; metabolism; endothelial dysfunction; fatty acid oxidation; AMPK-α
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Atawia, R.T.; Toque, H.A.; Meghil, M.M.; Benson, T.W.; Yiew, N.K.H.; Cutler, C.W.; Weintraub, N.L.; Caldwell, R.B.; Caldwell, R.W. Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice. Int. J. Mol. Sci. 2019, 20, 1462.

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