Arginase inhibition ameliorates hepatic metabolic abnormalities in obese mice.
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ABSTRACT: Objectives
We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity.Methods and results
After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visceral fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in lipid metabolism. Expression of phosphorylated 5' AMPK-activated protein kinase α was increased by arginase inhibition in the mouse livers and HepG2 cells.Conclusions
Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function.
SUBMITTER: Moon J
PROVIDER: S-EPMC4109998 | biostudies-literature |
REPOSITORIES: biostudies-literature
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