Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease

Miwa Kawanaka,1 Ken Nishino,1 Takahito Oka,1 Noriyo Urata,1 Jun Nakamura,1 Mitsuhiko Suehiro,1 Hirofumi Kawamoto,1 Yasutaka Chiba,2 Gotaro Yamada1 1Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan; 2Clinical Research Center, Kinki University Hospital, Sayama, Japan Objective: Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). Methods: In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). Results: Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion: Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH. Keywords: nonalcoholic steatohepatitis, amino acid imbalance, branched-chain amino acids, branched-chain amino acid-to-tyrosine ratio (BTR