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Review
. 2018 Nov 15;10(11):447.
doi: 10.3390/cancers10110447.

Lipid Metabolic Reprogramming in Hepatocellular Carcinoma

Hayato Nakagawa  1 , Yuki Hayata  2 , Satoshi Kawamura  3 , Tomoharu Yamada  4 , Naoto Fujiwara  5 , Kazuhiko Koike  6
Affiliations
Review

Lipid Metabolic Reprogramming in Hepatocellular Carcinoma

Hayato Nakagawa et al. Cancers (Basel). .

Abstract

Metabolic reprogramming for adaptation to the local environment has been recognized as a hallmark of cancer. Although alterations in fatty acid (FA) metabolism in cancer cells have received less attention compared to other metabolic alterations such as glucose or glutamine metabolism, recent studies have uncovered the importance of lipid metabolic reprogramming in carcinogenesis. Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC), and individuals with these conditions exhibit an increased intake of dietary FAs accompanied by enhanced lipolysis of visceral adipose tissue due to insulin resistance, resulting in enormous exogenous FA supplies to hepatocytes via the portal vein and lymph vessels. This "lipid-rich condition" is highly characteristic of obesity- and NASH-driven HCC. Although the way in which HCC cells adapt to such a condition and exploit it to aid their progression is not understood, we recently obtained new insights into this mechanism through lipid metabolic reprogramming. In addition, accumulating evidence supports the importance of lipid metabolic reprogramming in various situations of hepatocarcinogenesis. Thus, in this review, we discuss the latest findings regarding the role of FA metabolism pathways in hepatocarcinogenesis, focusing on obesity- and NASH-driven lipid metabolic reprogramming.

Keywords: carnitine palmitoyltransferase 2; fatty acid β-oxidation; hepatocellular carcinoma; metabolic reprogramming; non-alcoholic fatty liver disease; obesity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The pathways of lipid metabolism. FA: fatty acid; ACLY: ATP citrate lyase; ACC: acetyl-CoA carboxylase; FASN: fatty acid synthase; ACS: acyl-CoA synthetase; CPT1A: carnitine palmitoyltransferase 1A; CPT2: carnitine palmitoyltransferase 2; CACT: carnitine acylcarnitine translocase; SCD: stearoyl-CoA desaturase; GPAT: glycerol-3-phosphate acyltransferase; AGPAT: acylglycerolphosphate acyltransferase; MUFA: monounsaturated fatty acid; DGAT: diacylglycerol acyltransferase; DAG: diacylglycerol; TAG: triacylglycerol; TCA: tricarboxylic acid.
Figure 2
Figure 2
Two distinct lipid metabolic alterations in hepatocellular carcinoma (HCC). (A) Lipid metabolic reprograming in obesity- and nonalcoholic steatohepatitis (NASH)-related HCC. Fatty acid β-oxidation (FAO) is suppressed for adaptation to a lipid-rich environment. (B) Lipid metabolic reprograming in β-catenin-activated HCC. FAO is activated to fuel HCC.
See this image and copyright information in PMC

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