Semin Liver Dis 2022; 42(01): 077-086
DOI: 10.1055/s-0041-1731709
Review Article

Role of Lipogenesis Rewiring in Hepatocellular Carcinoma

Yi Zhou
1   Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
2   Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California
Junyan Tao
3   Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
4   Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
Diego F. Calvisi
5   Institute of Pathology, University of Regensburg, Germany
Xin Chen
2   Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California
› Author Affiliations


Metabolic rewiring is one of the hallmarks of cancer. Altered de novo lipogenesis is one of the pivotal metabolic events deregulated in cancers. Sterol regulatory element-binding transcription factor 1 (SREBP1) controls the transcription of major enzymes involved in de novo lipogenesis, including ACLY, ACACA, FASN, and SCD. Studies have shown the increased de novo lipogenesis in human hepatocellular carcinoma (HCC) samples. Multiple mechanisms, such as activation of the AKT/mechanistic target of rapamycin (mTOR) pathway, lead to high SREBP1 induction and the coordinated enhanced expression of ACLY, ACACA, FASN, and SCD genes. Subsequent functional analyses have unraveled these enzymes' critical role(s) and the related de novo lipogenesis in hepatocarcinogenesis. Importantly, targeting these molecules might be a promising strategy for HCC treatment. This paper comprehensively summarizes de novo lipogenesis rewiring in HCC and how this pathway might be therapeutically targeted.

Financial Support

This study is supported by NIH grants R01CA190606 and R01CA239251 to XC; P30DK026743 to UCSF Liver Center.

Publication History

Article published online:
26 July 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

  • References

  • 1 Sung H, Ferlay J, Siegel RL. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (03) 209-249
  • 2 Akinyemiju T, Abera S, Ahmed M. et al; Global Burden of Disease Liver Cancer Collaboration. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the Global Burden of Disease Study 2015. JAMA Oncol 2017; 3 (12) 1683-1691
  • 3 Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64 (01) 73-84
  • 4 Llovet JM, Ricci S, Mazzaferro V. et al; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359 (04) 378-390
  • 5 Huang A, Yang XR, Chung WY, Dennison AR, Zhou J. Targeted therapy for hepatocellular carcinoma. Signal Transduct Target Ther 2020; 5 (01) 146
  • 6 European Association for the Study of the Liver. Electronic address:, European Association for the Study of the Liver. Management of hepatocellular carcinoma. J Hepatol 2018; 69 (01) 182-236
  • 7 Kole C, Charalampakis N, Tsakatikas S. et al. Immunotherapy for hepatocellular carcinoma: a 2021 update. Cancers (Basel) 2020; 12 (10) 12
  • 8 Finn RS, Qin S, Ikeda M. et al; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020; 382 (20) 1894-1905
  • 9 Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell 2017; 169: 1327-1341
  • 10 Ahn SM, Jang SJ, Shim JH. et al. Genomic portrait of resectable hepatocellular carcinomas: implications of RB1 and FGF19 aberrations for patient stratification. Hepatology 2014; 60 (06) 1972-1982
  • 11 Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 2015; 149 (05) 1226.e4-1239.e4
  • 12 Raja A, Park I, Haq F, Ahn SM. FGF19-FGFR4 signaling in hepatocellular carcinoma. Cells 2019; 8 (06) 8
  • 13 Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab 2016; 23 (01) 27-47
  • 14 Vander Heiden MG, DeBerardinis RJ. Understanding the intersections between metabolism and cancer biology. Cell 2017; 168 (04) 657-669
  • 15 Che L, Paliogiannis P, Cigliano A, Pilo MG, Chen X, Calvisi DF. Pathogenetic, prognostic, and therapeutic role of fatty acid synthase in human hepatocellular carcinoma. Front Oncol 2019; 9: 1412
  • 16 Vaupel P, Schmidberger H, Mayer A. The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression. Int J Radiat Biol 2019; 95 (07) 912-919
  • 17 Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324 (5930): 1029-1033
  • 18 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144 (05) 646-674
  • 19 Mashima T, Seimiya H, Tsuruo T. De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br J Cancer 2009; 100 (09) 1369-1372
  • 20 Calvisi DF, Wang C, Ho C. et al. Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma. Gastroenterology 2011; 140 (03) 1071-1083
  • 21 Baenke F, Peck B, Miess H, Schulze A. Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech 2013; 6 (06) 1353-1363
  • 22 Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115 (05) 1343-1351
  • 23 Jensen-Urstad AP, Semenkovich CF. Fatty acid synthase and liver triglyceride metabolism: housekeeper or messenger?. Biochim Biophys Acta 2012; 1821 (05) 747-753
  • 24 Ameer F, Scandiuzzi L, Hasnain S, Kalbacher H, Zaidi N. De novo lipogenesis in health and disease. Metabolism 2014; 63 (07) 895-902
  • 25 Foufelle F, Ferré P. New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. Biochem J 2002; 366 (Pt 2): 377-391
  • 26 Dentin R, Girard J, Postic C. Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver. Biochimie 2005; 87 (01) 81-86
  • 27 Softic S, Cohen DE, Kahn CR. Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig Dis Sci 2016; 61 (05) 1282-1293
  • 28 Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep 2001; 2 (04) 282-286
  • 29 Iizuka K, Takao K, Yabe D. ChREBP-mediated regulation of lipid metabolism: involvement of the gut microbiota, liver, and adipose tissue. Front Endocrinol (Lausanne) 2020; 11: 587189
  • 30 Hollands MA, Cawthorne MA. Important sites of lipogenesis in the mouse other than liver and white adipose tissue. Biochem J 1981; 196 (02) 645-647
  • 31 Röhrig F, Schulze A. The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer 2016; 16 (11) 732-749
  • 32 Kuhajda FP. Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition 2000; 16 (03) 202-208
  • 33 Shimano H, Sato R. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology. Nat Rev Endocrinol 2017; 13 (12) 710-730
  • 34 Xu X, So JS, Park JG, Lee AH. Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP. Semin Liver Dis 2013; 33 (04) 301-311
  • 35 Guo D, Bell EH, Mischel P, Chakravarti A. Targeting SREBP-1-driven lipid metabolism to treat cancer. Curr Pharm Des 2014; 20 (15) 2619-2626
  • 36 Ettinger SL, Sobel R, Whitmore TG. et al. Dysregulation of sterol response element-binding proteins and downstream effectors in prostate cancer during progression to androgen independence. Cancer Res 2004; 64 (06) 2212-2221
  • 37 Du T, Sikora MJ, Levine KM. et al. Key regulators of lipid metabolism drive endocrine resistance in invasive lobular breast cancer. Breast Cancer Res 2018; 20 (01) 106
  • 38 Guo D, Prins RM, Dang J. et al. EGFR signaling through an Akt-SREBP-1-dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy. Sci Signal 2009; 2 (101) ra82
  • 39 Li C, Yang W, Zhang J. et al. SREBP-1 has a prognostic role and contributes to invasion and metastasis in human hepatocellular carcinoma. Int J Mol Sci 2014; 15 (05) 7124-7138
  • 40 Yamashita T, Honda M, Takatori H. et al. Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma. J Hepatol 2009; 50 (01) 100-110
  • 41 Ho C, Wang C, Mattu S. et al. AKT (v-akt murine thymoma viral oncogene homolog 1) and N-Ras (neuroblastoma ras viral oncogene homolog) coactivation in the mouse liver promotes rapid carcinogenesis by way of mTOR (mammalian target of rapamycin complex 1), FOXM1 (forkhead box M1)/SKP2, and c-Myc pathways. Hepatology 2012; 55 (03) 833-845
  • 42 Stiles B, Wang Y, Stahl A. et al. Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. Proc Natl Acad Sci U S A 2004; 101 (07) 2082-2087
  • 43 He L, Hou X, Kanel G. et al. The critical role of AKT2 in hepatic steatosis induced by PTEN loss. Am J Pathol 2010; 176 (05) 2302-2308
  • 44 Xu D, Wang Z, Xia Y. et al. The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis. Nature 2020; 580 (7804): 530-535
  • 45 Yu X, Lin Q, Wu Z. et al. ZHX2 inhibits SREBP1c-mediated de novo lipogenesis in hepatocellular carcinoma via miR-24-3p. J Pathol 2020; 252 (04) 358-370
  • 46 Heo MJ, Kang SH, Kim YS. et al. UBC12-mediated SREBP-1 neddylation worsens metastatic tumor prognosis. Int J Cancer 2020; 147 (09) 2550-2563
  • 47 Li N, Zhou ZS, Shen Y. et al. Inhibition of the sterol regulatory element-binding protein pathway suppresses hepatocellular carcinoma by repressing inflammation in mice. Hepatology 2017; 65 (06) 1936-1947
  • 48 Icard P, Wu Z, Fournel L, Coquerel A, Lincet H, Alifano M. ATP citrate lyase: a central metabolic enzyme in cancer. Cancer Lett 2020; 471: 125-134
  • 49 Han Q, Chen CA, Yang W. et al. ATP-citrate lyase regulates stemness and metastasis in hepatocellular carcinoma via the Wnt/β-catenin signaling pathway. Hepatobiliary Pancreat Dis Int 2021; 20 (03) 251-261
  • 50 Migita T, Narita T, Nomura K. et al. ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer. Cancer Res 2008; 68 (20) 8547-8554
  • 51 Gu L, Zhu Y, Lin X. et al. The IKKβ-USP30-ACLY axis controls lipogenesis and tumorigenesis. Hepatology 2021; 73 (01) 160-174
  • 52 Zheng Y, Zhou Q, Zhao C, Li J, Yu Z, Zhu Q. ATP citrate lyase inhibitor triggers endoplasmic reticulum stress to induce hepatocellular carcinoma cell apoptosis via p-eIF2α/ATF4/CHOP axis. J Cell Mol Med 2021; 25 (03) 1468-1479
  • 53 Hatzivassiliou G, Zhao F, Bauer DE. et al. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 2005; 8 (04) 311-321
  • 54 Yahagi N, Shimano H, Hasegawa K. et al. Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma. Eur J Cancer 2005; 41 (09) 1316-1322
  • 55 Ye B, Yin L, Wang Q, Xu C. ACC1 is overexpressed in liver cancers and contributes to the proliferation of human hepatoma Hep G2 cells and the rat liver cell line BRL 3A. Mol Med Rep 2019; 19 (05) 3431-3440
  • 56 Wang MD, Wu H, Fu GB. et al. Acetyl-coenzyme A carboxylase alpha promotion of glucose-mediated fatty acid synthesis enhances survival of hepatocellular carcinoma in mice and patients. Hepatology 2016; 63 (04) 1272-1286
  • 57 Fullerton MD, Galic S, Marcinko K. et al. Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med 2013; 19 (12) 1649-1654
  • 58 Lally JSV, Ghoshal S, DePeralta DK. et al. Inhibition of acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma. Cell Metab 2019; 29 (01) 174.e5-182.e5
  • 59 Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 2007; 7 (10) 763-777
  • 60 Hao Q, Li T, Zhang X. et al. Expression and roles of fatty acid synthase in hepatocellular carcinoma. Oncol Rep 2014; 32 (06) 2471-2476
  • 61 Graner E, Tang D, Rossi S. et al. The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell 2004; 5 (03) 253-261
  • 62 Gu L, Zhu Y, Lin X, Tan X, Lu B, Li Y. Stabilization of FASN by ACAT1-mediated GNPAT acetylation promotes lipid metabolism and hepatocarcinogenesis. Oncogene 2020; 39 (11) 2437-2449
  • 63 Gao Y, Lin LP, Zhu CH, Chen Y, Hou YT, Ding J. Growth arrest induced by C75, A fatty acid synthase inhibitor, was partially modulated by p38 MAPK but not by p53 in human hepatocellular carcinoma. Cancer Biol Ther 2006; 5 (08) 978-985
  • 64 Li L, Pilo GM, Li X. et al. Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans. J Hepatol 2016; 64 (02) 333-341
  • 65 Hu J, Che L, Li L. et al. Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice. Sci Rep 2016; 6: 20484
  • 66 Guri Y, Colombi M, Dazert E. et al. mTORC2 promotes tumorigenesis via lipid synthesis. Cancer Cell 2017; 32 (06) 807.e12-823.e12
  • 67 Zhang C, Sheng L, Yuan M. et al. Orlistat delays hepatocarcinogenesis in mice with hepatic co-activation of AKT and c-Met. Toxicol Appl Pharmacol 2020; 392: 114918
  • 68 Jia J, Che L, Cigliano A. et al. Pivotal role of fatty acid synthase in c-MYC driven hepatocarcinogenesis. Int J Mol Sci 2020; 21 (22) 21
  • 69 Che L, Chi W, Qiao Y. et al. Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans. Gut 2020; 69 (01) 177-186
  • 70 Igal RA. Stearoyl-CoA desaturase-1: a novel key player in the mechanisms of cell proliferation, programmed cell death and transformation to cancer. Carcinogenesis 2010; 31 (09) 1509-1515
  • 71 Bansal S, Berk M, Alkhouri N, Partrick DA, Fung JJ, Feldstein A. Stearoyl-CoA desaturase plays an important role in proliferation and chemoresistance in human hepatocellular carcinoma. J Surg Res 2014; 186 (01) 29-38
  • 72 Ma MKF, Lau EYT, Leung DHW. et al. Stearoyl-CoA desaturase regulates sorafenib resistance via modulation of ER stress-induced differentiation. J Hepatol 2017; 67 (05) 979-990
  • 73 Muir K, Hazim A, He Y. et al. Proteomic and lipidomic signatures of lipid metabolism in NASH-associated hepatocellular carcinoma. Cancer Res 2013; 73 (15) 4722-4731
  • 74 Li L, Wang C, Calvisi DF. et al. SCD1 Expression is dispensable for hepatocarcinogenesis induced by AKT and Ras oncogenes in mice. PLoS One 2013; 8 (09) e75104
  • 75 Zhao Y, Li M, Yao X. et al. HCAR1/MCT1 regulates tumor ferroptosis through the lactate-mediated AMPK-SCD1 activity and its therapeutic implications. Cell Rep 2020; 33 (10) 108487
  • 76 Qin XY, Su T, Yu W, Kojima S. Lipid desaturation-associated endoplasmic reticulum stress regulates MYCN gene expression in hepatocellular carcinoma cells. Cell Death Dis 2020; 11 (01) 66
  • 77 Chiang DY, Villanueva A, Hoshida Y. et al. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res 2008; 68 (16) 6779-6788
  • 78 Lee JS, Chu IS, Heo J. et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology 2004; 40 (03) 667-676
  • 79 Boyault S, Rickman DS, de Reyniès A. et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology 2007; 45 (01) 42-52
  • 80 Hoshida Y, Nijman SM, Kobayashi M. et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 2009; 69 (18) 7385-7392
  • 81 Rebouissou S, Nault JC. Advances in molecular classification and precision oncology in hepatocellular carcinoma. J Hepatol 2020; 72 (02) 215-229
  • 82 European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines on the management of benign liver tumours. J Hepatol 2016; 65 (02) 386-398
  • 83 Rebouissou S, Imbeaud S, Balabaud C. et al. HNF1alpha inactivation promotes lipogenesis in human hepatocellular adenoma independently of SREBP-1 and carbohydrate-response element-binding protein (ChREBP) activation. J Biol Chem 2007; 282 (19) 14437-14446
  • 84 Bluteau O, Jeannot E, Bioulac-Sage P. et al. Bi-allelic inactivation of TCF1 in hepatic adenomas. Nat Genet 2002; 32 (02) 312-315
  • 85 Mounier C, Bouraoui L, Rassart E. Lipogenesis in cancer progression (review). Int J Oncol 2014; 45 (02) 485-492
  • 86 Braig S. Chemical genetics in tumor lipogenesis. Biotechnol Adv 2018; 36 (06) 1724-1729
  • 87 Tang JJ, Li JG, Qi W. et al. Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and insulin resistance and reduces atherosclerotic plaques. Cell Metab 2011; 13 (01) 44-56
  • 88 Yin F, Feng F, Wang L, Wang X, Li Z, Cao Y. SREBP-1 inhibitor Betulin enhances the antitumor effect of Sorafenib on hepatocellular carcinoma via restricting cellular glycolytic activity. Cell Death Dis 2019; 10 (09) 672
  • 89 Chen Q, Wang T, Li J. et al. Effects of natural products on fructose-induced nonalcoholic fatty liver disease (NAFLD). Nutrients 2017; 9 (02) 9
  • 90 You Z, Li B, Xu J, Chen L, Ye H. Curcumin suppress the growth of hepatocellular carcinoma via down-regulating SREBF1 . Oncol Res 2018; (e-pub ahead of print) DOI: 10.3727/096504018 × 15219173841078.
  • 91 Vassallo A, Santoro V, Pappalardo I. et al. Liposome-mediated inhibition of inflammation by hydroxycitrate. Nanomaterials (Basel) 2020; 10 (10) 10
  • 92 Burke AC, Telford DE, Huff MW. Bempedoic acid: effects on lipoprotein metabolism and atherosclerosis. Curr Opin Lipidol 2019; 30 (01) 1-9
  • 93 Zaidi N, Swinnen JV, Smans K. ATP-citrate lyase: a key player in cancer metabolism. Cancer Res 2012; 72 (15) 3709-3714
  • 94 Pinkosky SL, Filippov S, Srivastava RA. et al. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. J Lipid Res 2013; 54 (01) 134-151
  • 95 Ruscica M, Banach M, Sahebkar A, Corsini A, Sirtori CR. ETC-1002 (Bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials. Expert Opin Pharmacother 2019; 20 (07) 791-803
  • 96 Li JJ, Wang H, Tino JA. et al. 2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors. Bioorg Med Chem Lett 2007; 17 (11) 3208-3211
  • 97 Alkhouri N. NASH and NAFLD: emerging drugs, therapeutic targets and translational and clinical challenges. Expert Opin Investig Drugs 2020; 29 (02) 87
  • 98 Fhu CW, Ali A. Fatty acid synthase: an emerging target in cancer. Molecules 2020; 25 (17) 25
  • 99 Menendez JA, Lupu R. Fatty acid synthase (FASN) as a therapeutic target in breast cancer. Expert Opin Ther Targets 2017; 21 (11) 1001-1016
  • 100 You BJ, Hour MJ, Chen LY, Luo SC, Hsu PH, Lee HZ. Fenofibrate induces human hepatoma Hep3B cells apoptosis and necroptosis through inhibition of thioesterase domain of fatty acid synthase. Sci Rep 2019; 9 (01) 3306
  • 101 Tracz-Gaszewska Z, Dobrzyn P. Stearoyl-CoA desaturase 1 as a therapeutic target for the treatment of cancer. Cancers (Basel) 2019; 11 (07) 11
  • 102 Huang GM, Jiang QH, Cai C, Qu M, Shen W. SCD1 negatively regulates autophagy-induced cell death in human hepatocellular carcinoma through inactivation of the AMPK signaling pathway. Cancer Lett 2015; 358 (02) 180-190
  • 103 Yao Y, Sun S, Wang J. et al. Canonical Wnt signaling remodels lipid metabolism in zebrafish hepatocytes following Ras oncogenic insult. Cancer Res 2018; 78 (19) 5548-5560
  • 104 Syed-Abdul MM, Parks EJ, Gaballah AH. et al. Fatty acid synthase inhibitor TVB-2640 reduces hepatic de novo lipogenesis in males with metabolic abnormalities. Hepatology 2020; 72 (01) 103-118
  • 105 Stiede K, Miao W, Blanchette HS. et al. Acetyl-coenzyme A carboxylase inhibition reduces de novo lipogenesis in overweight male subjects: a randomized, double-blind, crossover study. Hepatology 2017; 66 (02) 324-334
  • 106 Wei X, Song H, Yin L. et al. Fatty acid synthesis configures the plasma membrane for inflammation in diabetes. Nature 2016; 539 (7628): 294-298
  • 107 Broadfield LA, Pane AA, Talebi A, Swinnen JV, Fendt SM. Lipid metabolism in cancer: new perspectives and emerging mechanisms. Dev Cell 2021; 56 (10) 1363-1393
  • 108 Lochner M, Berod L, Sparwasser T. Fatty acid metabolism in the regulation of T cell function. Trends Immunol 2015; 36 (02) 81-91
  • 109 Everts B, Amiel E, Huang SC. et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation. Nat Immunol 2014; 15 (04) 323-332
  • 110 Berod L, Friedrich C, Nandan A. et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med 2014; 20 (11) 1327-1333
  • 111 Huang SC, Everts B, Ivanova Y. et al. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol 2014; 15 (09) 846-855
  • 112 Cao D, Song X, Che L. et al. Both de novo synthetized and exogenous fatty acids support the growth of hepatocellular carcinoma cells. Liver Int 2017; 37 (01) 80-89
  • 113 Nelson ME, Lahiri S, Chow JD. et al. Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival. Nat Commun 2017; 8: 14689
  • 114 Che L, Pilo MG, Cigliano A. et al. Oncogene dependent requirement of fatty acid synthase in hepatocellular carcinoma. Cell Cycle 2017; 16 (06) 499-507
  • 115 Beckner ME, Fellows-Mayle W, Zhang Z. et al. Identification of ATP citrate lyase as a positive regulator of glycolytic function in glioblastomas. Int J Cancer 2010; 126 (10) 2282-2295
  • 116 Ismail A, Doghish AS, Elsadek BEM, Salama SA, Mariee AD. Hydroxycitric acid potentiates the cytotoxic effect of tamoxifen in MCF-7 breast cancer cells through inhibition of ATP citrate lyase. Steroids 2020; 160: 108656
  • 117 Evaluation of major cardiovascular events in patients with, or at high risk for, cardiovascular disease who are statin intolerant treated with bempedoic acid (ETC-1002) or placebo (CLEAR Outcomes). Accessed June 15, 2021 at:
  • 118 Study to evaluate the pharmacodynamic effects of a single oral dose of GS-0976 (NDI-010976) in healthy adult subjects. Accessed June 15, 2020 at:
  • 119 Evaluation of 3-V Bioscience-2640 to reduce de novo lipogenesis in subjects with characteristics of metabolic syndrome. Accessed June 15, 2021 at:
  • 120 A study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MK8245 (8245–004)(COMPLETED). Accessed June 15, 2021 at: