GS-0976 (Firsocostat): an investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH)

Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes

Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016) · Hepatology · doi:10.1002/hep.28431 · Cited by 10,781

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases

Chalasani, N., Younossi, Z., Lavine, J. E., Charlton, M., Cusi, K., Rinella, M., Harrison, S. A., Brunt, E. M., & Sanyal, A. J. (2018) · Hepatology · doi:10.1002/hep.29367 · Cited by 7,239

Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease

Donnelly, K. L., Smith, C. I., Schwarzenberg, S. J., Jessurun, J., Boldt, M. D., & Parks, E. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23621 · Cited by 3,604

Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

Sanyal, A. J., Chalasani, N., Kowdley, K. V., McCullough, A., Diehl, A. M., Bass, N. M., Neuschwander-Tetri, B. A., Lavine, J. E., Tonascia, J., Unalp, A., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907929 · Cited by 3,327

Mechanisms of Insulin Action and Insulin Resistance

Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028

Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease

Angulo, P., Kleiner, D. E., Dam-Larsen, S., Adams, L. A., Bjornsson, E. S., Charatcharoenwitthaya, P., Mills, P. R., Keach, J. C., Lafferty, H. D., Stahler, A., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.043 · Cited by 2,987

Fibrosis stage is the strongest predictor for disease‐specific mortality in NAFLD after up to 33 years of follow‐up

Ekstedt, M., Hagström, H., Nasr, P., Fredrikson, M., Stål, P., Kechagias, S., & Hultcrantz, R. (2015) · Hepatology · doi:10.1002/hep.27368 · Cited by 2,287

Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): A multicentre, randomised, placebo-controlled trial

Neuschwander-Tetri, B. A., Loomba, R., Sanyal, A. J., Lavine, J. E., Van Natta, M. L., Abdelmalek, M. F., Chalasani, N., Dasarathy, S., Diehl, A. M., Hameed, B., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61933-4 · Cited by 2,237

Fibrosis Progression in Nonalcoholic Fatty Liver vs Nonalcoholic Steatohepatitis: A Systematic Review and Meta-analysis of Paired-Biopsy Studies

Singh, S., Allen, A. M., Wang, Z., Prokop, L. J., Murad, M. H., & Loomba, R. (2015) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2014.04.014 · Cited by 1,748

Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease

Lambert, J. E., Ramos–Roman, M. A., Browning, J. D., & Parks, E. J. (2014) · Gastroenterology · doi:10.1053/j.gastro.2013.11.049 · Cited by 1,069 · cited 1×

Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial

Cusi, K., Orsak, B., Bril, F., Lomonaco, R., Hecht, J., Ortiz-Lopez, C., Tio, F., Hardies, J., Darland, C., Musi, N., et al. (2016) · Annals of Internal Medicine · doi:10.7326/m15-1774 · Cited by 1,024

Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin

Fullerton, M. D., Galic, S., Marcinko, K., Sikkema, S., Pulinilkunnil, T., Chen, Z.-P., O'Neill, H. M., Ford, R. J., Palanivel, R., O'Brien, M., et al. (2013) · Nature Medicine · doi:10.1038/nm.3372 · Cited by 893

Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases

Samuel, V. T., & Shulman, G. I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.002 · Cited by 745 · cited 1×

Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes

Perry, R. J., Camporez, J.-P. G., Kursawe, R., Titchenell, P. M., Zhang, D., Perry, C. J., Jurczak, M. J., Abudukadier, A., Han, M. S., Zhang, X.-M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.012 · Cited by 719

Hepatocellular carcinoma in the absence of cirrhosis in United States Veterans is associated with nonalcoholic fatty liver disease

Mittal, S., El-Serag, H. B., Sada, Y. H., Kanwal, F., Duan, Z., Temple, S., May, S. B., Kramer, J. R., Richardson, P. A., & Davila, J. A. (2016) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2015.07.019 · Cited by 648

NASH Leading Cause of Liver Transplant in Women: Updated Analysis of Indications For Liver Transplant and Ethnic and Gender Variances

Noureddin, M., Vipani, A., Bresee, C. J., Todo, T., Kim, I. K., Alkhouri, N., Setiawan, V. W., Tran, T. T., Ayoub, W. S., Lu, S. C.-L., et al. (2018) · The American Journal of Gastroenterology · doi:10.1038/s41395-018-0088-6 · Cited by 578

Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery

Tong, L. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5121-4 · Cited by 526

The subcellular localization of acetyl-CoA carboxylase 2

Abu-Elheiga, L. A., Brinkley, W. R., Zhong, L., Chirala, S. S., Woldegiorgis, G., & Wakil, S. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1444 · Cited by 450

Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2

Savage, D. B. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27300 · Cited by 447

Acetyl CoA carboxylase inhibition reduces hepatic steatosis but elevates plasma triglycerides in mice and humans: a bedside to bench investigation

Kim, C.-W., Addy, C., Kusunoki, J., Anderson, N. N., Deja, S., Fu, X., Burgess, S. C., Li, C., Ruddy, M., Chakravarthy, M., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.009 · Cited by 419

Inhibition of Acetyl-CoA Carboxylase by Phosphorylation or the Inhibitor ND-654 Suppresses Lipogenesis and Hepatocellular Carcinoma

Lally, J., Ghoshal, S., DePeralta, D. K., Moaven, O., Wei, L., Masia, R., Erstad, D. J., Fujiwara, N., Leong, V., Houde, V. P., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.08.020 · Cited by 417

Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal

Alkhouri, N., Dixon, L. J., & Feldstein, A. E. (2009) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.09.32 · Cited by 413

REGULATION OF MAMMALIAN ACETYL-COENZYME A CARBOXYLASE

Kim, K.-H. (1997) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.17.1.77 · Cited by 395

Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets

Abu-Elheiga, L., Oh, W., Kordari, P., & Wakil, S. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1733877100 · Cited by 389

Simtuzumab Is Ineffective for Patients With Bridging Fibrosis or Compensated Cirrhosis Caused by Nonalcoholic Steatohepatitis

Harrison, S. A., Abdelmalek, M. F., Caldwell, S., Shiffman, M. L., Diehl, A. M., Ghalib, R., Lawitz, E. J., Rockey, D. C., Schall, R. A., Jia, C., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.07.006 · Cited by 384

Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver

Dongiovanni, P., Stender, S., Pietrelli, A., Mancina, R. M., Cespiati, A., Petta, S., Pelusi, S., Pingitore, P., Badiali, S., Maggioni, M., et al. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12719 · Cited by 367

GS-0976 Reduces Hepatic Steatosis and Fibrosis Markers in Patients With Nonalcoholic Fatty Liver Disease

Loomba, R., Kayali, Z., Noureddin, M., Ruane, P., Lawitz, E. J., Bennett, M., Wang, L., Harting, E., Tarrant, J. M., McColgan, B. J., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.07.027 · Cited by 340

Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: The multiethnic cohort

Setiawan, V. W., Stram, D. O., Porcel, J., Lu, S. C.-L., Marchand, L. L., & Noureddin, M. (2016) · Hepatology · doi:10.1002/hep.28677 · Cited by 302

Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats

Harriman, G., Greenwood, J., Bhat, S., Huang, X., Wang, R., Paul, D., Tong, L., Saha, A. K., Westlin, W. F., Kapeller, R., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520686113 · Cited by 287

Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis

Mao, J., DeMayo, F. J., Li, H., Abu-Elheiga, L., Gu, Z., Shaikenov, T. E., Kordari, P., Chirala, S. S., Heird, W. C., & Wakil, S. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603115103 · Cited by 285

Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats

Perry, R. J., Zhang, D., Zhang, X.-M., Boyer, J. L., & Shulman, G. I. (2015) · Science · doi:10.1126/science.aaa0672 · Cited by 283

Structural Basis for Double-Sieve Discrimination of L-Valine from L-Isoleucine and L-Threonine by the Complex of tRNAVal and Valyl-tRNA Synthetase

Fukai, S., Nureki, O., Sekine, S., Shimada, A., Tao, J., Vassylyev, D. G., & Yokoyama, S. (2000) · Cell · doi:10.1016/s0092-8674(00)00182-3 · Cited by 264

Acetyl‐CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents

Goedeke, L., Bates, J. G., Vatner, D. F., Perry, R. J., Wang, T., Ramírez, R., Li, L., Ellis, M. W., Zhang, D., Wong, K. E., et al. (2018) · Hepatology · doi:10.1002/hep.30097 · Cited by 261

Prevalence of Nonalcoholic Steatohepatitis-Associated Cirrhosis in the United States: An Analysis of National Health and Nutrition Examination Survey Data

Kabbany, M. N., Selvakumar, P. K. C., Watt, K. D. S., López, R., Akras, Z., Zein, N. N., Carey, W., & Alkhouri, N. (2017) · The American Journal of Gastroenterology · doi:10.1038/ajg.2017.5 · Cited by 247

Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

Vatner, D. F., Majumdar, S. K., Kumashiro, N., Petersen, M. C., Rahimi, Y., Gattu, A. K., Bears, M., Camporez, J.-P. G., Cline, G. W., Jurczak, M. J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1423952112 · Cited by 235

Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis

Lawitz, E. J., Coste, A., Poordad, F., Alkhouri, N., Loo, N., McColgan, B. J., Tarrant, J. M., Nguyen, T., Han, L., Chung, C., et al. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.04.042 · Cited by 217

Acetyl-coenzyme A carboxylases: versatile targets for drug discovery

Tong, L., & Harwood, H. J. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21077 · Cited by 207

Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms.

Abu-Elheiga, L. A., Jayakumar, A., Baldini, A., Chirala, S. S., & Wakil, S. J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.9.4011 · Cited by 189

Nonalcoholic Fatty Liver Disease, Diabetes, Obesity, and Hepatocellular Carcinoma

Noureddin, M., & Rinella, M. E. (2015) · Clinics in Liver Disease · doi:10.1016/j.cld.2015.01.012 · Cited by 185

Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis

Mohamad, B., Shah, V., Onyshchenko, M., Elshamy, M., Aucejo, F., Lopez, R., Hanouneh, I. A., Alhaddad, R., & Alkhouri, N. (2016) · Hepatology International · doi:10.1007/s12072-015-9679-0 · Cited by 166

Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis

Patel, J. R., Bettencourt, R., Cui, J. Y., Salotti, J., Hooker, J. C., Bhatt, A., Hernandez, C., Nguyen, P., Aryafar, H., Valasek, M. A., et al. (2016) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x16656735 · Cited by 163

Acute or chronic upregulation of mitochondrial fatty acid oxidation has no net effect on whole-body energy expenditure or adiposity

Hoehn, K. L., Turner, N., Swarbrick, M. M., Wilks, D., Preston, E., Phua, Y., Joshi, H., Furler, S. M., Larance, M., Hegarty, B. D., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.11.008 · Cited by 156

Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis

Kim, C.-W., Moon, Y.-A., Park, S. W., Cheng, D., Kwon, H. J., & Horton, J. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001292107 · Cited by 136

Acetyl‐coenzyme A carboxylase inhibition reduces de novo lipogenesis in overweight male subjects: A randomized, double‐blind, crossover study

Stiede, K., Miao, W., Blanchette, H., Beysen, C., Harriman, G. C. B., Harwood, H. J., Kelley, H., Kapeller, R., Schmalbach, T., & Westlin, W. (2017) · Hepatology · doi:10.1002/hep.29246 · Cited by 115

Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake

Olson, D. P., Pulinilkunnil, T., Cline, G. W., Shulman, G. I., & Lowell, B. B. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913492107 · Cited by 109

Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation

Kim, C.-W., Addy, C., Kusunoki, J., Anderson, N. N., Deja, S., Fu, X., Burgess, S. C., Cai, L., Ruddy, M., Chakravarthy, M. V., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.011 · Cited by 105

AMPK-ACC signaling modulates platelet phospholipids and potentiates thrombus formation

Lepropre, S., Kautbally, S., Octave, M., Ginion, A., Onselaer, M.-B., Steinberg, G. R., Kemp, B. E., Hego, A., Wéra, O., Brouns, S. L. N., et al. (2018) · Blood · doi:10.1182/blood-2018-02-831503 · Cited by 92

Acetyl-CoA Carboxylase 2−/− Mutant Mice are Protected against Fatty Liver under High-fat, High-carbohydrate Dietary and de Novo Lipogenic Conditions

Abu-Elheiga, L. A., Wu, H., Gu, Z., BRESSLER, R. C., & Wakil, S. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.309559 · Cited by 85

Stearoyl-CoA desaturase plays an important role in proliferation and chemoresistance in human hepatocellular carcinoma

Bansal, S., Berk, M. P., Alkhouri, N., Partrick, D. A., Fung, J. J., & Feldstein, A. E. (2013) · Journal of Surgical Research · doi:10.1016/j.jss.2013.07.001 · Cited by 76

Isoforms of acetyl-CoA carboxylase: structures, regulatory properties and metabolic functions

Brownsey, R. W., Zhande, R., & Boone, A. N. (1997) · Biochemical Society Transactions · doi:10.1042/bst0251232 · Cited by 71

The dynamic organization of fungal acetyl-CoA carboxylase

Hunkeler, M., Stuttfeld, E., Hagmann, A., Imseng, S., & Maier, T. (2016) · Nature Communications · doi:10.1038/ncomms11196 · Cited by 56

GS-06-Positive Results from REGENERATE: A Phase 3 International, Randomized, Placebo-Controlled Study Evaluating Obeticholic Acid Treatment for NASH

Younossi, Z. M., Ratziu, V., Loomba, R. S., Rinella, M. E., Anstee, Q. M., Goodman, Z. D., Bédossa, P., Geier, A., Beckebaum, S., Newsome, P. N., et al. (2019) · Journal of Hepatology · doi:10.1016/s0618-8278(19)30006-4 · Cited by 55

A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice

Abulizi, A., Perry, R. J., Camporez, J. P. G., Jurczak, M. J., Petersen, K. F., Aspichueta, P., & Shulman, G. I. (2017) · The FASEB Journal · doi:10.1096/fj.201700001r · Cited by 41

Metabolism of immune cells in cancer

Leone, R. D., & Powell, J. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-020-0273-y · Cited by 877

Lipid metabolism in cancer: New perspectives and emerging mechanisms

Broadfield, L. A., Pane, A. A., Talebi, A., Swinnen, J. V., & Fendt, S. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.04.013 · Cited by 793

Metabolic-associated fatty liver disease and lipoprotein metabolism

Heeren, J., & Scheja, L. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101238 · Cited by 692

The intricate relationship between type 2 diabetes mellitus (T2DM), insulin resistance (IR), and nonalcoholic fatty liver disease (NAFLD)

Tanase, D. M., Gosav, E. M., Costea, C. F., Ciocoiu, M., Lacatusu, C. M., Maranduca, M. A., Ouatu, A., & Floria, M. (2020) · Journal of Diabetes Research · doi:10.1155/2020/3920196 · Cited by 627

Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity

Yoon, H., Shaw, J. L., Haigis, M. C., & Greka, A. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.08.027 · Cited by 538

Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis

Lawitz, E. J., Coste, A., Poordad, F., Alkhouri, N., Loo, N., McColgan, B. J., Tarrant, J. M., Nguyen, T., Han, L., Chung, C., et al. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.04.042 · Cited by 217

GS-0976 Reduces Hepatic Steatosis and Fibrosis Markers in Patients With Nonalcoholic Fatty Liver Disease

Loomba, R., Kayali, Z., Noureddin, M., Ruane, P., Lawitz, E. J., Bennett, M., Wang, L., Harting, E., Tarrant, J. M., McColgan, B. J., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.07.027 · Cited by 340

Acetyl-CoA carboxylase inhibitor increases LDL-apoB production rate in NASH with cirrhosis: prevention by fenofibrate

Dandan, M., Han, J., Mann, S., Kim, R., Li, K. W., Mohammed, H., Chuang, J.-C., Zhu, K., Billin, A. N., Huss, R. S., et al. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100339 · Cited by 18

New avenues for NASH therapy by targeting ACC

Bian, H., Liu, Y.-M., & Chen, Z. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.001 · Cited by 19

Combinations of an acetyl CoA carboxylase inhibitor with hepatic lipid modulating agents do not augment antifibrotic efficacy in preclinical models of NASH and fibrosis

Vijayakumar, A., Ökesli, A., Wang, T., Olson, I. A., Seung, M., Kusam, S., Hollenback, D., Mahadevan, S., Marchand, B., Toteva, M. M., et al. (2022) · Hepatology Communications · doi:10.1002/hep4.2011 · Cited by 14