title: The influence of pioglitazone on the plasma amino acid profile in patients with nonalcoholic steatohepatitis (NASH).
abstract: OBJECTIVE
  The peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand, piglitazone, enhances the degradation of branched-chain amino acids (BCAAs) in adipose tissue. However, it remains unknown whether pioglitazone influences the plasma amino acids (AA) profile in patients with nonalcoholic steatohepatitis (NASH). Thus, we investigated the relation between the therapeutic effect and the AA profile in NASH patients with a prospective study.
  
  
  METHODS
  We randomized 25 histologically proven NASH patients to diet treatment only or diet treatment plus pioglitazone (15 mg/day), and investigated the biological data for 24 months. We measured the concentrations of AAs and compared them between the beginning and the end of the study.
  
  
  RESULTS
  Compared with the diet only group, pioglitazone therapy was associated with an increase in body weight (mean change -1.03 vs. +3.8 kg; p = 0.027) and subcutaneous fat (-3.7 vs. +45.7 cm(2); p = 0.056), and decreased ALT levels (-0.6 vs. -38.4 IU/L; p = 0.029) and HbA1c (0.33 vs. -0.29 %; p = 0.016). Regarding the AA profile, L-isoleucine, L-leucine, L-histidine, and L-lysine were significantly reduced in patients treated with pioglitazone. Furthermore, L-leucine was significantly reduced compared with those in the diet only group (mean change -34.8 vs. +4.12 nmol/mL; p = 0.032). Interestingly, there was a significant correlation between the changes in BCAAs, especially L-leucine, and those in ALT regardless of treatment with pioglitazone.
  
  
  CONCLUSIONS
  Pioglitazone therapy in NASH subjects significantly reduced the plasma BCAA level and the degradation was closely related to the improvement of the ALT levels. These results suggest that pioglitazone improves insulin resistance and BCAA metabolism in NASH patients.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574, Japan. kakazu@coral.ocn.ne.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakazu
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ninomiya
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kimura
authors.affiliation: Department of Gastroenterology, Sendai City Hospital, 3-1, Shimizukoji, Wakabayashiku, Sendai, Miyagi, 984-8501, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nagasaki
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
keywords: Branched-chain amino acids; Nonalcoholic steatohepatitis; PPAR-γ; Pioglitazone