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Asymmetric Dimethylarginine Levels in the Plasma Are Elevated in Non‐Alcoholic Fatty Liver Disease
Author(s) -
Kasumov Takhar,
Edmison John M.,
Bennett Carole,
Dasarathy Srinivasan,
Lopez Rocio,
McCullough Arthur J.,
Kalhan Satish C.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.709.2
Subject(s) - medicine , asymmetric dimethylarginine , insulin resistance , steatohepatitis , endocrinology , fatty liver , steatosis , insulin , chemistry , arginine , disease , biochemistry , amino acid
Asymmetrical dimethylarginine (ADMA) and symmetrical dimethylarginine (SDMA) are produced by the breakdown of proteins that have been methylated post translationally at an arginine residue. Plasma levels of ADMA are elevated in insulin resistant states. ADMA is metabolized in the liver, while SDMA cleared by the kidney. Non‐alcoholic fatty liver disease (NAFLD) is the most common liver disease in humans and is associated with insulin resistance. We hypothesized that plasma levels of ADMA will be increased in subjects with NAFLD and with the progression of NAFLD from hepatic steatosis to non alcoholic steatohepatitis (NASH). Plasma levels of ADMA and SDMA were measured by HPLC in 48 patients with histologically confirmed NAFLD (16 steatosis and 32 NASH) and 29 healthy controls. Estimates of kidney function in all subjects were in normal range. Plasma ADMA levels were significantly higher (P<0.002) in patients with NAFLD compared with controls. SDMA levels were not different between any groups. ADMA/SDMA ratio was significantly higher in patients with NASH compared with controls (1.7±0.5 vs. 1.4±0.3, p<0.05). Estimates of insulin resistance as measured by HOMA, did not correlate with plasma levels of ADMA or SDMA. ADMA/SDMA ratio correlated with plasma insulin levels and with insulin resistance. We conclude that ADMA and ADMA/SDMA ratio can be used as an additional biomarker of NASH in combination with measures of insulin resistance. Since ADMA is an inhibitor of nitric oxide synthase, high levels of ADMA in NASH may contribute to the vascular abnormalities in NASH.