Hepatol Int. 2013 Jun;7(2):577-85. doi: 10.1007/s12072-012-9395-y. Epub 2012 Aug 14.
The influence of pioglitazone on the plasma amino acid profile in patients with nonalcoholic steatohepatitis (NASH).
Hepatology international
Eiji Kakazu, Yasuteru Kondo, Masashi Ninomiya, Osamu Kimura, Futoshi Nagasaki, Yoshiyuki Ueno, Tooru Shimosegawa
Affiliations
Affiliations
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574, Japan. [email protected].
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574, Japan.
- Department of Gastroenterology, Sendai City Hospital, 3-1, Shimizukoji, Wakabayashiku, Sendai, Miyagi, 984-8501, Japan.
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
PMID: 26201790
DOI: 10.1007/s12072-012-9395-y
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 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.
Keywords: Branched-chain amino acids; Nonalcoholic steatohepatitis; PPAR-γ; Pioglitazone
References
- Anal Biochem. 1982 Nov 15;127(1):17-24 - PubMed
- Hepatology. 2003 Apr;37(4):917-23 - PubMed
- Metabolism. 1991 Jan;40(1):51-8 - PubMed
- N Engl J Med. 1969 Oct 9;281(15):811-6 - PubMed
- J Hepatol. 2010 Feb;52(2):206-10 - PubMed
- J Gastroenterol. 2008;43(9):720-8 - PubMed
- Cell Metab. 2009 Apr;9(4):311-26 - PubMed
- Biochem Int. 1991 Dec;25(5):797-806 - PubMed
- Diabetes Care. 2011 Apr;34(4):916-22 - PubMed
- Gastroenterology. 2002 Jun;122(7):1924-40 - PubMed
- Dig Liver Dis. 2008 May;40(5):371-8 - PubMed
- J Immunol. 2007 Nov 15;179(10):7137-46 - PubMed
- Hepatology. 2005 Jun;41(6):1313-21 - PubMed
- Gut. 1982 May;23(5):362-70 - PubMed
- N Engl J Med. 2006 Nov 30;355(22):2297-307 - PubMed
- Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1552-63 - PubMed
- Gastroenterology. 2008 Oct;135(4):1176-84 - PubMed
- J Clin Invest. 2003 Aug;112(4):608-18 - PubMed
- Diabetes. 1997 Sep;46(9):1393-9 - PubMed
- Mayo Clin Proc. 1980 Jul;55(7):434-8 - PubMed
- Hepatology. 2010 Jan;51(1):121-9 - PubMed
- BMJ. 2010 Mar 23;340:c332 - PubMed
- Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18745-50 - PubMed
- Hepatology. 2008 Nov;48(5):1718-23 - PubMed
- N Engl J Med. 2010 May 6;362(18):1675-85 - PubMed
- Gut. 1978 Nov;19(11):1068-73 - PubMed
- Hepatology. 2008 Feb;47(2):592-5 - PubMed
- Diabetes Care. 2011 Jun;34(6):1369-71 - PubMed
- Nat Med. 2011 Apr;17(4):448-53 - PubMed
- Hepatology. 2008 Feb;47(2):380-4 - PubMed
- J Clin Endocrinol Metab. 2002 Jun;87(6):2784-91 - PubMed
- Am J Clin Nutr. 2008 May;87(5):1141-7 - PubMed
- Am J Clin Nutr. 2007 Aug;86(2):285-300 - PubMed
- Hepatology. 2008 Aug;48(2):442-8 - PubMed
- Hepatology. 2009 Dec;50(6):1936-45 - PubMed
- Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E164-74 - PubMed
- J Clin Invest. 2007 Jun;117(6):1658-69 - PubMed
- Biochem Biophys Res Commun. 2004 Feb 27;315(1):187-95 - PubMed
- Diabetes. 2001 Aug;50(8):1863-71 - PubMed
- Cell. 1998 Apr 17;93(2):241-52 - PubMed
Publication Types