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Age-related increase in alanine aminotransferase correlates with elevated levels of plasma amino acids, decanoylcarnitine, Lp-PLA2 Activity, oxidative stress, and arterial stiffness.

Abstract
We investigated plasma metabolite profiles that correlated with age-related serum alanine aminotransferase (ALT) levels. The study included 602 healthy, nondiabetic subjects (aged 30-65 years); 393 individuals had normal ALT levels at baseline. Fifty-three (13.5%) individuals developed elevated ALT levels after 3 years. The remaining 340 subjects with normal ALT were matched to the elevated-ALT group (n = 53) for age, gender, BMI, fasting glucose, and ALT to form the control group (n = 53). At the 3-year follow-up, the elevated-ALT group exhibited greater increases in waist circumference, serum free fatty acid, ALT, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), bilirubin, plasma oxidized LDL, Lp-PLA2 activity, urinary 8-epi-prostaglandin F2α (8-epi-PGF2α), and brachial-ankle pulse-wave velocity (ba-PWV) compared to the control group after baseline adjustment. The elevated-ALT group exhibited greater increases in plasma l-valine (q = 0.036), l-leucine (q = 0.012), l-phenylalanine (q = 0.012), and decanoylcarnitine (q = 0.002). Mean ALT levels positively correlated with changes in these four metabolites, which correlated with changes in AST, GGT, Lp-PLA2 activity, urinary 8-epi-PGF2α, and ba-PWV. Mean ALT changes did not significantly correlate with HOMA-insulin resistance. These results suggest that increased plasma levels of l-valine, l-leucine, l-phenylalanine, and decanoylcarnitine precede insulin resistance during periods of elevated ALT. This metabolic disturbance coincides with enhanced risk factors for cardiovascular disease.
AuthorsSaem Jung, Oh Yoen Kim, Minjoo Kim, Juheui Song, Sang-Hyun Lee, Jong Ho Lee
JournalJournal of proteome research (J Proteome Res) Vol. 13 Issue 7 Pg. 3467-75 (Jul 03 2014) ISSN: 1535-3907 [Electronic] United States
PMID24874467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amino Acids
  • Biomarkers
  • decanoylcarnitine
  • Alanine Transaminase
  • Carnitine
Topics
  • Adult
  • Aged
  • Aging (blood)
  • Alanine Transaminase (blood)
  • Amino Acids (blood)
  • Biomarkers (blood)
  • Carnitine (analogs & derivatives, blood)
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress
  • Prospective Studies
  • Vascular Stiffness

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