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.