Role of arginase 2 in systemic metabolic activity and adipose tissue fatty acid metabolism in diet-induced obese mice

Reem T. Atawia, Haroldo Alfredo Flores Toque, Mohamed M. Meghil, Tyler W. Benson, Nicole K.H. Yiew, Christopher W Cutler, Neal Lee Weintraub, Ruth B Caldwell, Robert William Caldwell

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1462
JournalInternational journal of molecular sciences
Volume20
Issue number6
DOIs
StatePublished - Mar 2 2019

Fingerprint

adipose tissues
Arginase
Obese Mice
diets
sucrose
fats
Sugar (sucrose)
metabolism
fatty acids
Nutrition
Oils and fats
Fatty acids
varespladib methyl
Metabolism
mice
Sucrose
Adipose Tissue
Fatty Acids
Fats
Tissue

Keywords

  • AMPK-α
  • Arginase
  • Endothelial dysfunction
  • Fatty acid oxidation
  • Inflammation
  • Metabolism
  • Obesity

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

@article{3bbec6d53fbd436aaf26498259b22ff8,
title = "Role of arginase 2 in systemic metabolic activity and adipose tissue fatty acid metabolism in diet-induced obese mice",
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.",
keywords = "AMPK-α, Arginase, Endothelial dysfunction, Fatty acid oxidation, Inflammation, Metabolism, Obesity",
author = "Atawia, {Reem T.} and {Flores Toque}, {Haroldo Alfredo} and Meghil, {Mohamed M.} and Benson, {Tyler W.} and Yiew, {Nicole K.H.} and Cutler, {Christopher W} and Weintraub, {Neal Lee} and Caldwell, {Ruth B} and Caldwell, {Robert William}",
year = "2019",
month = "3",
day = "2",
doi = "10.3390/ijms20061462",
language = "English (US)",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",

}

TY - JOUR

T1 - Role of arginase 2 in systemic metabolic activity and adipose tissue fatty acid metabolism in diet-induced obese mice

AU - Atawia, Reem T.

AU - Flores Toque, Haroldo Alfredo

AU - Meghil, Mohamed M.

AU - Benson, Tyler W.

AU - Yiew, Nicole K.H.

AU - Cutler, Christopher W

AU - Weintraub, Neal Lee

AU - Caldwell, Ruth B

AU - Caldwell, Robert William

PY - 2019/3/2

Y1 - 2019/3/2

N2 - 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.

AB - 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.

KW - AMPK-α

KW - Arginase

KW - Endothelial dysfunction

KW - Fatty acid oxidation

KW - Inflammation

KW - Metabolism

KW - Obesity

UR - http://www.scopus.com/inward/record.url?scp=85063767638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063767638&partnerID=8YFLogxK

U2 - 10.3390/ijms20061462

DO - 10.3390/ijms20061462

M3 - Article

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 6

M1 - 1462

ER -