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The influence of pioglitazone on the plasma amino acid profile in patients with nonalcoholic steatohepatitis (NASH)

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Abstract

Background and aims

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 cm2; 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.

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Acknowledgements

This work was supported by Grant-in-Aid for Young Scientists (B), no. 23790762, from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and grants from Ministry of Health, Labor, and Welfare of Japan. We thank Chikako Sato for excellent technical assistance.

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Authors and Affiliations

  1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574, Japan

    Eiji Kakazu, Yasuteru Kondo, Masashi Ninomiya, Osamu Kimura & Tooru Shimosegawa

  2. Department of Gastroenterology, Sendai City Hospital, 3-1, Shimizukoji, Wakabayashiku, Sendai, Miyagi, 984-8501, Japan

    Futoshi Nagasaki

  3. Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan

    Yoshiyuki Ueno

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  1. Eiji Kakazu
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  2. Yasuteru Kondo
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  3. Masashi Ninomiya
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  4. Osamu Kimura
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  5. Futoshi Nagasaki
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  6. Yoshiyuki Ueno
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  7. Tooru Shimosegawa
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Correspondence to Eiji Kakazu.

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12072_2012_9395_MOESM1_ESM.pdf

Supplementary Material A linear regression model was used to model the variation in the plasma ALT changes and the plasma amino acid changes. Among all 20 kinds of free amino acids, only the changes in l-leucine and l-tyrosine were significantly correlated with the ALT changes in patients with NASH. ΔALT is expressed in IU/L and the amino acid changes are expressed in nmol/mL. (PDF 318 kb)

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Kakazu, E., Kondo, Y., Ninomiya, M. et al. The influence of pioglitazone on the plasma amino acid profile in patients with nonalcoholic steatohepatitis (NASH). Hepatol Int 7, 577–585 (2013). https://doi.org/10.1007/s12072-012-9395-y

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  • DOI: https://doi.org/10.1007/s12072-012-9395-y

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