Branched chain amino acids are associated with the heterogeneity of the area of lipid droplets in hepatocytes of patients with non-alcoholic fatty liver disease

Eiji Kakazu, Akitoshi Sano, Tatsuki Morosawa, Jun Inoue, Masashi Ninomiya, Tomoaki Iwata, Takuya Nakamura, Satoshi Takai, Shojiro Sawada, Hideki Katagiri, Tooru Shimosegawa, Atsushi Masamune

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Aim: Macrovesicular steatosis around the central vein (zone 3) is one of the pathological features of non-alcoholic fatty liver disease or steatohepatitis (NAFLD/NASH). The aim of this study is to elucidate precisely the association between the area of lipid droplets (LDs) and the plasma metabolic parameters in patients with NAFLD/NASH. Methods: Eighty patients with NAFLD/NASH diagnosed by needle biopsy were enrolled. The LDs around zone 3 were counted automatically by image processing software, the total area of LDs (TLDs), the maximum area of LDs (MAXLDs), the average area of LDs (AVELDs) and the heterogeneity by the coefficient of variation (CV [%]) were quantified. The correlations between these values and plasma metabolic parameters were analyzed. We evaluated the association between branched chain amino acids (BCAAs) and the heterogeneity of LDs in hepatocytes in vitro and in vivo. Results: The MAXLDs was significantly correlated with more metabolic parameters than AVELDs and TLDs. The level of BCAAs was independently associated with the CV among the metabolic parameters. In early stage NAFLD, aspartate and alanine aminotransferase were significantly higher in the high CV group than in the low CV group. The high concentration of BCAAs increased the CV of LDs in hepatocytes accompanied by the expression of phosphor-p70 S6 kinase and sterol regulatory element-binding protein 1 in vitro. A high BCAA diet induced high heterogeneity of LDs around zone 3 in ob/ob mice. Conclusions: The levels of BCAAs were associated with the LD heterogeneity of hepatocytes around zone 3 in patients with NAFLD/NASH.

Original languageEnglish
Pages (from-to)860-871
Number of pages12
JournalHepatology Research
Volume49
Issue number8
DOIs
Publication statusPublished - 2019 Aug 1

Keywords

  • BCAA
  • NAFLD
  • NASH
  • lipid droplet
  • steatosis

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

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