Metabolic Alteration in Hepatocellular Carcinoma: Mechanism of Lipid Accumulation in Well-Differentiated Hepatocellular Carcinoma

Objective. Metabolic alteration is widely considered as one of the hallmarks of cancer. Hepatocellular carcinoma (HCC) presents a unique pathological feature in which lipid accumulation is common in well-differentiated HCC and rare in poorly differentiated HCC; however, the underlying mechanism rema...

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Main Authors: Hideo Suzuki, Motoyuki Kohjima, Masatake Tanaka, Takeshi Goya, Shinji Itoh, Tomoharu Yoshizumi, Masaki Mori, Mariko Tsuda, Motoi Takahashi, Miho Kurokawa, Koji Imoto, Shigeki Tashiro, Akifumi Kuwano, Masaki Kato, Seiji Okada, Makoto Nakamuta, Yoshihiro Ogawa
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Canadian Journal of Gastroenterology and Hepatology
Online Access:http://dx.doi.org/10.1155/2021/8813410
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author Hideo Suzuki
Motoyuki Kohjima
Masatake Tanaka
Takeshi Goya
Shinji Itoh
Tomoharu Yoshizumi
Masaki Mori
Mariko Tsuda
Motoi Takahashi
Miho Kurokawa
Koji Imoto
Shigeki Tashiro
Akifumi Kuwano
Masaki Kato
Seiji Okada
Makoto Nakamuta
Yoshihiro Ogawa
author_facet Hideo Suzuki
Motoyuki Kohjima
Masatake Tanaka
Takeshi Goya
Shinji Itoh
Tomoharu Yoshizumi
Masaki Mori
Mariko Tsuda
Motoi Takahashi
Miho Kurokawa
Koji Imoto
Shigeki Tashiro
Akifumi Kuwano
Masaki Kato
Seiji Okada
Makoto Nakamuta
Yoshihiro Ogawa
author_sort Hideo Suzuki
collection DOAJ
description Objective. Metabolic alteration is widely considered as one of the hallmarks of cancer. Hepatocellular carcinoma (HCC) presents a unique pathological feature in which lipid accumulation is common in well-differentiated HCC and rare in poorly differentiated HCC; however, the underlying mechanism remains unclear. Methods. Tissue samples were obtained from 103 HCC patients who had undergone hepatic resection and 12 living donors of liver transplantation. We evaluated metabolic gene expressions in cancer tissues as well as background noncancer tissues and compared the expressions by the degree of cancer differentiation and by liver disease states. Besides, the metabolomics was evaluated and integrated to gene expressions in nonalcoholic steatohepatitis (NASH)-HCC model mice. Results. In cancer tissues, the expression levels of enzymes related to glycolysis, pentose phosphate pathway (PPP), and fatty acid (FA) synthesis were increased and that of tricarboxylic acid (TCA) cycle and β-oxidation were suppressed. Same metabolic alterations were observed in noncancer tissue as the liver disease progresses from healthy liver to chronic hepatitis, cirrhosis, and HCC. Similar alterations of metabolic genes were detected in NASH-HCC mice, which were consistent with the results of metabolomics. As the degree of cancer differentiation decreased, glycolysis and PPP were accelerated; however, FA synthesis and uptake were diminished. Conclusions. The metabolic alterations including glycolysis, PPP, TCA cycle, and β-oxidation became more prominent as liver disease progresses from normal, chronic hepatitis, cirrhosis, well-, moderately, and poorly differentiated HCC. FA synthesis and uptake were highest in well-differentiated HCC, which could explain the lipid accumulation.
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spelling doaj-art-0dd370627150485da6c33cc6ea90e6342025-02-03T05:51:11ZengWileyCanadian Journal of Gastroenterology and Hepatology2291-27892291-27972021-01-01202110.1155/2021/88134108813410Metabolic Alteration in Hepatocellular Carcinoma: Mechanism of Lipid Accumulation in Well-Differentiated Hepatocellular CarcinomaHideo Suzuki0Motoyuki Kohjima1Masatake Tanaka2Takeshi Goya3Shinji Itoh4Tomoharu Yoshizumi5Masaki Mori6Mariko Tsuda7Motoi Takahashi8Miho Kurokawa9Koji Imoto10Shigeki Tashiro11Akifumi Kuwano12Masaki Kato13Seiji Okada14Makoto Nakamuta15Yoshihiro Ogawa16Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Pathophysiology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Gastroenterology, Kyushu Medical Center, National Hospital Organization, 1-8-1 Zigyohama, Chuo-ku, Fukuoka 810-8563, JapanDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanObjective. Metabolic alteration is widely considered as one of the hallmarks of cancer. Hepatocellular carcinoma (HCC) presents a unique pathological feature in which lipid accumulation is common in well-differentiated HCC and rare in poorly differentiated HCC; however, the underlying mechanism remains unclear. Methods. Tissue samples were obtained from 103 HCC patients who had undergone hepatic resection and 12 living donors of liver transplantation. We evaluated metabolic gene expressions in cancer tissues as well as background noncancer tissues and compared the expressions by the degree of cancer differentiation and by liver disease states. Besides, the metabolomics was evaluated and integrated to gene expressions in nonalcoholic steatohepatitis (NASH)-HCC model mice. Results. In cancer tissues, the expression levels of enzymes related to glycolysis, pentose phosphate pathway (PPP), and fatty acid (FA) synthesis were increased and that of tricarboxylic acid (TCA) cycle and β-oxidation were suppressed. Same metabolic alterations were observed in noncancer tissue as the liver disease progresses from healthy liver to chronic hepatitis, cirrhosis, and HCC. Similar alterations of metabolic genes were detected in NASH-HCC mice, which were consistent with the results of metabolomics. As the degree of cancer differentiation decreased, glycolysis and PPP were accelerated; however, FA synthesis and uptake were diminished. Conclusions. The metabolic alterations including glycolysis, PPP, TCA cycle, and β-oxidation became more prominent as liver disease progresses from normal, chronic hepatitis, cirrhosis, well-, moderately, and poorly differentiated HCC. FA synthesis and uptake were highest in well-differentiated HCC, which could explain the lipid accumulation.http://dx.doi.org/10.1155/2021/8813410
spellingShingle Hideo Suzuki
Motoyuki Kohjima
Masatake Tanaka
Takeshi Goya
Shinji Itoh
Tomoharu Yoshizumi
Masaki Mori
Mariko Tsuda
Motoi Takahashi
Miho Kurokawa
Koji Imoto
Shigeki Tashiro
Akifumi Kuwano
Masaki Kato
Seiji Okada
Makoto Nakamuta
Yoshihiro Ogawa
Metabolic Alteration in Hepatocellular Carcinoma: Mechanism of Lipid Accumulation in Well-Differentiated Hepatocellular Carcinoma
Canadian Journal of Gastroenterology and Hepatology
title Metabolic Alteration in Hepatocellular Carcinoma: Mechanism of Lipid Accumulation in Well-Differentiated Hepatocellular Carcinoma
title_full Metabolic Alteration in Hepatocellular Carcinoma: Mechanism of Lipid Accumulation in Well-Differentiated Hepatocellular Carcinoma
title_fullStr Metabolic Alteration in Hepatocellular Carcinoma: Mechanism of Lipid Accumulation in Well-Differentiated Hepatocellular Carcinoma
title_full_unstemmed Metabolic Alteration in Hepatocellular Carcinoma: Mechanism of Lipid Accumulation in Well-Differentiated Hepatocellular Carcinoma
title_short Metabolic Alteration in Hepatocellular Carcinoma: Mechanism of Lipid Accumulation in Well-Differentiated Hepatocellular Carcinoma
title_sort metabolic alteration in hepatocellular carcinoma mechanism of lipid accumulation in well differentiated hepatocellular carcinoma
url http://dx.doi.org/10.1155/2021/8813410
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