Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease
Open accessAbstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess liver triacylglycerol (TAG), inflammation, and liver damage. The goal of the present study was to directly quantify the biological sources of hepatic and plasma lipoprotein TAG in NAFLD. Patients (5 male and 4 female; 44 +/- 10 years of age) scheduled for a medically indicated liver biopsy were infused with and orally fed stable isotopes for 4 days to label and track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo lipogenesis (DNL) pathway, present in liver tissue and lipoprotein TAG. Hepatic and lipoprotein TAG fatty acids were analyzed by gas chromatography/mass spectrometry. NAFLD patients were obese, with fasting hypertriglyceridemia and hyperinsulinemia. Of the TAG accounted for in liver, 59.0% +/- 9.9% of TAG arose from NEFAs; 26.1% +/- 6.7%, from DNL; and 14.9% +/- 7.0%, from the diet. The pattern of labeling in VLDL was similar to that in liver, and throughout the 4 days of labeling, the liver demonstrated reciprocal use of adipose and dietary fatty acids. DNL was elevated in the fasting state and demonstrated no diurnal variation. These quantitative metabolic data document that both elevated peripheral fatty acids and DNL contribute to the accumulation of hepatic and lipoprotein fat in NAFLD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Although the major source of hepatocellular triglycerides are adipose tissue-derived NEFA, the rate of hepatic de novo lipogenesis is also much greater in MASLD, further contributing to intrahepatic lipid accumulation.
“Of note, although the major source of hepatocellular triglycerides are adipose tissue-derived NEFA, the rate of hepatic de novo lipogenesis is also much greater in MASLD, further contributing to intrahepatic lipid accumulation [17].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [17]
The Abstract and Discussion report that serum NEFAs were the largest source of liver triglyceride fatty acids (59%) and that de novo lipogenesis contributed substantially (26%) in the studied NAFLD patients. The Discussion describes lipogenesis as markedly elevated in the fasting state and contributing to liver fat, but says it did not increase after meals. The unqualified claim that its rate is much greater in MASLD extends beyond the fasting-state finding. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe major fraction of hepatocellular triglycerides in people with obesity and MASLD is not derived from non-esterified fatty acids (NEFA) provided by dietary lipids, but from circulating NEFA released from adipose tissue.
“Remarkably, the major fraction of hepatocellular triglycerides in people with obesity and MASLD is not derived from non-esterified fatty acids (NEFA) provided by dietary lipids, but from circulating NEFA released from adipose tissue [17].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [17]
In individuals with MASLD and obesity, hepatic triglyceride is reported to derive approximately 59% from circulating free fatty acids, 26% from de novo lipogenesis, and 15% from dietary sources.
“In individuals with MASLD and obesity, hepatic TG is reported to derive approximately 59% from circulating FFAs, 26% from DNL, and 15% from dietary sources [67].”
From Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications (2025) · cites this paper as [67]
In a study by Donnelly et al., IHTG was composed mainly of FFAs from SAT lipolysis (~60%) and, to a lesser extent, FFAs from DNL (~25%) or diet (~15%).
“IHTG was composed mainly of FFAs from SAT lipolysis (∼60%) and, to a lesser extent, FFAs from DNL (∼25%) or diet (∼15%).”
From Lipid metabolism in MASLD and MASH: From mechanism to the clinic (2024) · cites this paper as [23]
Sarcopenic obesity seems to impair insulin signaling in hepatocytes, resulting in increased de novo hepatic lipogenesis and inhibited hepatic β-oxidation.
“Sarcopenic obesity seems to impair insulin signaling in hepatocytes, resulting in increased de novo hepatic lipogenesis and inhibited hepatic β-oxidation [141].”
From Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences (2020) · cites this paper as [141]
Hepatic lipid accumulation occurs in response to uptake of circulating free fatty acids, de novo lipogenesis in the liver, or dietary fats.
“Hepatic lipid accumulation occurs in response to uptake of circulating free fatty acids (FFAs), de novo lipogenesis in the liver, or dietary fats (2)”
From Development of an in vitro human liver system for interrogating nonalcoholic steatohepatitis (2016) · cites this paper as [2]
The increase in VLDL-TG secretion rate in obese subjects who have NAFLD is primarily caused by the availability of nonsystemic fatty acids derived from lipolysis of IHTG, not VAT.
“Our data suggest that the increase in VLDL-TG secretion rate in obese subjects who have NAFLD is primarily caused by the availability of nonsystemic fatty acids derived from lipolysis of IHTG, not VAT, because VAT volume was the same in both groups and de novo lipogenesis accounts for up to 20% of the fatty acids secreted in VLDL-TG in subjects with NAFLD (39,40).”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [40]
De novo lipogenesis accounts for up to 20% of the fatty acids secreted in VLDL-TG in subjects with NAFLD.
“de novo lipogenesis accounts for up to 20% of the fatty acids secreted in VLDL-TG in subjects with NAFLD (39,40).”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [40]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · see citing works
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · see citing works
Toprak, Ö., Kurt, H., Sarı, Y., Şarkış, C., Us, H., & Kırık, A. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000468530 · Cited by 29,769 · see citing works
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15593 · Cited by 4,285 · see citing works
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092 · see citing works
Ludwig, J., Viggiano, T. R., McGill, D. B., & Ott, B. J. (1980) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(24)00530-5 · Cited by 2,903 · see citing works
Nonalcoholic Fatty Liver Disease
Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Bugianesi, E., Lenzi, M., McCullough, A. J., Natale, S., Forlani, G., & Melchionda, N. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1844 · Cited by 2,581 · see citing works
Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities
Sanyal, A. J., Campbell–Sargent, C., Mirshahi, F., Rizzo, W. B., Contos, M. J., Sterling, R. K., Luketic, V. A., Shiffman, M. L., & Clore, J. N. (2001) · Gastroenterology · doi:10.1053/gast.2001.23256 · Cited by 2,078 · see citing works
Association of nonalcoholic fatty liver disease with insulin resistance
Marchesini, G., Brizi, M., Morselli‐Labate, A. M., Bianchi, G. P., Bugianesi, E., McCullough, A. J., Forlani, G., & Melchionda, N. (1999) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00271-5 · Cited by 1,564 · see citing works
Dixon, J. B., Bhathal, P. S., & O’Brien, P. E. (2001) · Gastroenterology · doi:10.1053/gast.2001.25540 · Cited by 1,365 · see citing works
Nonalcoholic steatohepatitis: An expanded clinical entity
Bacon, B. R., Farahvash, M. J., Janney, C. G., & Neuschwander‐Tetri, B. A. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90235-6 · Cited by 1,137 · see citing works
AGA technical review on nonalcoholic fatty liver disease
Sanyal, A. J. (2002) · Gastroenterology · doi:10.1053/gast.2002.36572 · Cited by 1,072 · see citing works
Nonalcoholic fatty liver disease
Clark, J. M., Brancati, F. L., & Diehl, A. M. (2002) · Gastroenterology · doi:10.1053/gast.2002.33573 · Cited by 926 · see citing works
Abdominal Fat: Standardized Technique for Measurement at CT
Yoshizumi, T., Nakamura, T., Yamane, M., Islam, A. H. M. W., Menju, M., Yamasaki, K., Arai, T., Kotani, K., Funahashi, T., Yamashita, S., et al. (1999) · Radiology · doi:10.1148/radiology.211.1.r99ap15283 · Cited by 829 · see citing works
Brodie, S. E. (1996) · Survey of Ophthalmology · doi:10.1016/s0039-6257(96)80075-0 · Cited by 770 · see citing works
A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis
Promrat, K., Lutchman, G., Uwaifo, G. I., Freedman, R. J., Soza, A., Heller, T., Doo, E., Ghany, M., Premkumar, A., Park, Y., et al. (2004) · Hepatology · doi:10.1002/hep.20012 · Cited by 726 · cited 1× · see citing works
“Indeed, NAFLD patients treated with insulin-sensitizing agents show marked improvement in their condition (28, 30, 31).”
BackgroundMetformin in non-alcoholic steatohepatitis.
Marchesini, G., Bianchi, G., Tomassetti, S., Zoli, M., & Melchionda, N. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06042-1 · Cited by 682 · see citing works
Nonalcoholic steatohepatitis: A study of 49 patients
Lee, R. G. (1989) · Human Pathology · doi:10.1016/0046-8177(89)90249-9 · Cited by 547 · see citing works
Schwarz, J.-M., Linfoot, P., Dare, D., & Aghajanian, K. (2003) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.1.43 · Cited by 496 · see citing works
Diraison, F., Moulin, P., & Beylot, M. (2003) · Diabetes & Metabolism · doi:10.1016/s1262-3636(07)70061-7 · Cited by 435 · see citing works
Radioactive and Stable Isotope Tracers in Biomedicine
Bramlet, R. C. (1993) · Clinical Nuclear Medicine · doi:10.1097/00003072-199305000-00027 · Cited by 396 · see citing works
A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis.
Caldwell, S. H., Hespenheide, E. E., Redick, J. A., Iezzoni, J. C., Battle, E. H., & Sheppard, B. L. (2001) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.03553.x · Cited by 394 · see citing works
Parks, E. J., Krauss, R. M., Christiansen, M. P., Neese, R. A., & Hellerstein, M. K. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6572 · Cited by 350 · see citing works
Self-citationApolipoprotein synthesis in nonalcoholic steatohepatitis
Charlton, M., Raghavakaimal, S., Rasmussen, D. L., Lindor, K. D., & Nair, S. K. (2002) · Hepatology · doi:10.1053/jhep.2002.32527 · Cited by 332 · see citing works
Bajaj, M., Suraamornkul, S., Pratipanawatr, T., Hardies, L. J., Pratipanawatr, W., Glass, L. C., Cersósimo, E., Miyazaki, Y., & DeFronzo, R. A. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1364 · Cited by 291 · see citing works
Non‐alcoholic steatohepatitis: another disease of affluence
James, *., & Day, C. (1999) · The Lancet · doi:10.1016/s0140-6736(99)00163-4 · Cited by 271 · see citing works
Kinetics of triglyceride turnover of very low density lipoproteins of human plasma
Reaven, G. M., Hill, D. B., Gross, R. C., & Farquhar, J. W. (1965) · Journal of Clinical Investigation · doi:10.1172/jci105290 · Cited by 221 · see citing works
Hudgins, L. C., Hellerstein, M. K., Seidman, C. E., Neese, R. A., Tremaroli, J. D., & Hirsch, J. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32407-x · Cited by 216 · see citing works
Persistent hyperaminotransferasemia resolving after weight reduction in obese children
Vajro, P., Fontanella, A., Perna, C., Orso, G., Tedesco, M., & Vincenzo, A. D. (1994) · The Journal of Pediatrics · doi:10.1016/s0022-3476(94)70202-0 · Cited by 193 · see citing works
Farquhar, J. W., Gross, R. C., Wagner, R. M., & Reaven, G. M. (1965) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39649-8 · Cited by 189 · see citing works
Chen, Y. I., Golay, A., Swislocki, A., & Reaven, G. M. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-64-1-17 · Cited by 178 · see citing works
Temporal pattern of de novo lipogenesis in the postprandial state in healthy men1–3
Timlin, M. T., & Parks, E. J. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.1.35 · Cited by 170 · see citing works
Self-citationAbdominal fat assessed by computed tomography: Sex difference in distribution
Dixon, A. K. (1983) · Clinical Radiology · doi:10.1016/s0009-9260(83)80303-1 · Cited by 124 · see citing works
Systemic and Forearm Triglyceride Metabolism
Miles, J. M., Park, Y., Walewicz, D., Russell-Lopez, C., Windsor, S. L., Isley, W. L., Coppack, S. W., & Harris, W. S. (2004) · Diabetes · doi:10.2337/diabetes.53.3.521 · Cited by 114 · see citing works
Insulin resistance, adipose tissue and coronary heart disease
Frayn, K. N., & Coppack, S. W. (1992) · Clinical Science · doi:10.1042/cs0820001 · Cited by 100 · see citing works
Investigation of in vivo fatty acid metabolism in AFABP/aP2−/−mice
Baar, R. A., Dingfelder, C. S., Smith, L. A., Bernlohr, D., Wu, C., Lange, A. J., & Parks, E. J. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00256.2004 · Cited by 98 · see citing works
Self-citationE.J.*, P. (2002) · British Journal Of Nutrition · doi:10.1079/bjnbjn/2002544 · Cited by 92 · see citing works
Parks, E. J. (2002) · British Journal Of Nutrition · doi:10.1079/bjn/2002544 · Cited by 82 · see citing works
Self-citationDonnelly, K. L., Margosian, M. R., Parks, E. J., Sheth, S. S., & Lusis, A. J. (2004) · Journal of Nutrition · doi:10.1093/jn/134.6.1475 · Cited by 64 · see citing works
Self-citationKooner, J. S., Baliga, R. R., Wilding, J. P. H., Crook, D., Packard, C. J., Banks, L. M., Peart, S., Aitman, T. J., & Scott, J. (1998) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.18.7.1021 · Cited by 61 · see citing works
Hepatic Catabolism of Remnant Lipoproteins: Where the Action Is
Havel, R. J., & Hamilton, R. L. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000115382.53810.24 · Cited by 58 · see citing works
Boberg, J., Carlson, L. A., & FREYSCHUSS, U. (1972) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1972.tb00580.x · Cited by 57 · see citing works
Hellerstein, M. K., Neese, R. A., & Schwarz, J. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.265.5.e814 · Cited by 56 · see citing works
Use of stable isotopically labeled tracers for studies of metabolic kinetics: An overview
Patterson, B. W. (1997) · Metabolism · doi:10.1016/s0026-0495(97)90260-2 · Cited by 54 · see citing works
Methods for measurement of fatty acid and cholesterol metabolism
Hellerstein, M. K. (1995) · Current Opinion in Lipidology · doi:10.1097/00041433-199506000-00010 · Cited by 36 · see citing works
Nilsson, S., & Scherstén, T. (1969) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365516909080159 · Cited by 33 · see citing works
The use of computers to study rates of lipid metabolism
Baker, N. (1969) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42644-6 · Cited by 33 · see citing works
Marzetta, C. A., Foster, D., & Brunzell, J. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42737-3 · Cited by 30 · see citing works
LIPID COMPOSITION OF HUMAN LIVER BIOPSY SPECIMENS
LAURELL, S., & Lundquist, A. (1971) · Acta Medica Scandinavica · doi:10.1111/j.0954-6820.1971.tb04339.x · Cited by 29 · see citing works
Nitrogen, Lipid, Glycogen and Deoxyribonucleic Acid Content of Human Liver
Martinsson, A., Sunzel, H., & HOOD, B. (1963) · Acta Medica Scandinavica · doi:10.1111/j.0954-6820.1963.tb17461.x · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354 · see citing works
Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism
Morrison, D. J., & Preston, T. (2016) · Gut Microbes · doi:10.1080/19490976.2015.1134082 · Cited by 3,781 · see citing works
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 · see citing works
Rinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023) · Hepatology · doi:10.1097/hep.0000000000000323 · Cited by 2,667 · see citing works
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis
Tilg, H., & Moschen, A. R. (2010) · Hepatology · doi:10.1002/hep.24001 · Cited by 2,548 · see citing works
Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications
Fabbrini, E., Sullivan, S., & Klein, S. (2010) · Hepatology · doi:10.1002/hep.23280 · Cited by 2,100 · see citing works
Cornier, M.-A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., & Eckel, R. H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0024 · Cited by 2,162 · see citing works
Human Fatty Liver Disease: Old Questions and New Insights
Cohen, J. C., Horton, J. D., & Hobbs, H. H. (2011) · Science · doi:10.1126/science.1204265 · Cited by 2,089 · see citing works
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066 · see citing works
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002 · see citing works
Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis
Anstee, Q. M., Targher, G., & Day, C. P. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.41 · Cited by 1,747 · see citing works
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529 · see citing works
A lipidomic analysis of nonalcoholic fatty liver disease
Puri, P., Baillie, R. A., Wiest, M. M., Mirshahi, F., Choudhury, J., Cheung, O., Sargeant, C., Contos, M. J., & Sanyal, A. J. (2007) · Hepatology · doi:10.1002/hep.21763 · Cited by 1,338 · see citing works
The integrative biology of type 2 diabetes
Roden, M., & Shulman, G. I. (2019) · Nature · doi:10.1038/s41586-019-1797-8 · Cited by 1,167 · see citing works
Disordered lipid metabolism and the pathogenesis of insulin resistance.
Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007) · Physiological Reviews · doi:10.1152/physrev.00024.2006 · Cited by 1,107 · see citing works
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 · see citing works
Self-citationNeuschwander‐Tetri, B. A. (2010) · Hepatology · doi:10.1002/hep.23719 · Cited by 1,077 · see citing works
The role of the gut microbiota in NAFLD
Leung, C., Rivera, L., Furness, J. B., & Angus, P. W. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.85 · Cited by 1,020 · see citing works
Tilg, H., Moschen, A. R., & Roden, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.147 · Cited by 1,002 · see citing works
Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Fabbrini, E., Magkos, F., Mohammed, B. S., Pietka, T., Abumrad, N. A., Patterson, B. W., Okunade, A., & Klein, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904944106 · Cited by 972 · see citing works
Why does obesity cause diabetes?
Klein, S., Gastaldelli, A., Yki-Järvinen, H., & Scherer, P. E. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.012 · Cited by 939 · see citing works
Insulin resistance: a metabolic pathway to chronic liver disease
Bugianesi, E., McCullough, A. J., & Marchesini, G. (2005) · Hepatology · doi:10.1002/hep.20920 · Cited by 900 · see citing works
Nonalcoholic Fatty Liver Disease: Pathology and Pathogenesis
Tiniakos, D. G., Vos, M. B., & Brunt, E. M. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102132 · Cited by 870 · see citing works
Lipotoxicity and the gut-liver axis in NASH pathogenesis
Marra, F., & Svegliati-Baroni, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.014 · Cited by 847 · see citing works
Adiels, M., Olofsson, S.-O., Taskinen, M.-R., & Borén, J. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.160192 · Cited by 820 · see citing works
Kim, K. H., Jeong, Y. T., Oh, H., Kim, S. H., Cho, J. M., Kim, Y.-N., Kim, S. S., Kim, D. H., Hur, K. Y., Kim, H. K., et al. (2013) · Nature Medicine · doi:10.1038/nm.3014 · Cited by 774 · see citing works
The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome
Lim, J. S., Mietus-Snyder, M., Valente, A., Schwarz, J.-M., & Lustig, R. H. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.41 · Cited by 771 · see citing works
Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease
Smith, G. I., Shankaran, M., Yoshino, M., Schweitzer, G. G., Chondronikola, M., Beals, J. W., Okunade, A. L., Patterson, B. W., Nyangau, E., Field, T., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci134165 · Cited by 771 · see citing works
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 · see citing works
Kammoun, H. L., Chabanon, H., Hainault, I., Luquet, S., Magnan, C., Koike, T., Ferré, P., & Foufelle, F. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37007 · Cited by 732 · see citing works
Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease
Softic, S., Cohen, D. E., & Kahn, C. R. (2016) · Digestive Diseases and Sciences · doi:10.1007/s10620-016-4054-0 · Cited by 709 · see citing works
Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease
Jiang, C., Xie, C., Li, F., Zhang, L., Nichols, R. G., Krausz, K. W., Cai, J., Qi, Y., Fang, Z.-Z., Takahashi, S., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci76738 · Cited by 693 · see citing works
Overproduction of large VLDL particles is driven by increased liver fat content in man
Adiels, M., Taskinen, M.-R., Packard, C., Caslake, M. J., Soro-Paavonen, A., Westerbacka, J., Vehkavaara, S., Häkkinen, A., Olofsson, S.-O., Yki-Järvinen, H., et al. (2006) · Diabetologia · doi:10.1007/s00125-005-0125-z · Cited by 690 · see citing works
Sunny, N. E., Parks, E. J., Browning, J. D., & Burgess, S. C. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.11.004 · Cited by 672 · see citing works
Self-citationFabbrini, E., Mohammed, B. S., Magkos, F., Korenblat, K. M., Patterson, B. W., & Klein, S. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.11.038 · Cited by 631 · see citing works
Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance
Meex, R. C. R., & Watt, M. J. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.56 · Cited by 631 · see citing works
The Liver as an Endocrine Organ—Linking NAFLD and Insulin Resistance
Watt, M. J., Miotto, P. M., De Nardo, W., & Montgomery, M. K. (2019) · Endocrine Reviews · doi:10.1210/er.2019-00034 · Cited by 615 · see citing works
Cancello, R., Tordjman, J., Poitou, C., Guilhem, G., Bouillot, J. L., Hugol, D., Coussieu, C., Basdevant, A., Hen, A. B., Bedossa, P., et al. (2006) · Diabetes · doi:10.2337/db06-0133 · Cited by 607 · see citing works
Immune cell-mediated features of non-alcoholic steatohepatitis
Huby, T., & Gautier, E. L. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00639-3 · Cited by 573 · see citing works
Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease
Mota, M., Banini, B. A., Cazanave, S. C., & Sanyal, A. J. (2016) · Metabolism · doi:10.1016/j.metabol.2016.02.014 · Cited by 570 · see citing works
Recent insights into the pathogenesis of nonalcoholic fatty liver disease
Arab, J. P., Arrese, M., & Trauner, M. (2018) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043617 · Cited by 573 · see citing works
Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate
Zhao, S., Jang, C., Liu, J., Uehara, K., Gilbert, M., Izzo, L., Zeng, X., Trefely, S., Fernandez, S., Carrer, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2101-7 · Cited by 553 · see citing works
A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer
Asgharpour, A., Cazanave, S. C., Pacana, T., Seneshaw, M., Vincent, R., Banini, B. A., Kumar, D. P., Daita, K., Min, H.-K., Mirshahi, F., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.05.005 · Cited by 538 · see citing works
Lipid accumulation in non-adipose tissue and lipotoxicity
van Herpen, N. A., & Schrauwen-Hinderling, V. B. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.11.049 · Cited by 500 · see citing works
Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1α transcription coactivator
Li, X., Monks, B., Ge, Q., & Birnbaum, M. J. (2007) · Nature · doi:10.1038/nature05861 · Cited by 487 · see citing works
Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests
Masoodi, M., Gastaldelli, A., Hyötyläinen, T., Arretxe, E., Alonso, C., Gaggini, M., Brosnan, J., Anstee, Q. M., Millet, O., Ortiz, P., et al. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00502-9 · Cited by 451 · see citing works
Luukkonen, P. K., Zhou, Y., Sädevirta, S., Leivonen, M., Arola, J., Orešič, M., Hyötyläinen, T., & Yki-Järvinen, H. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.01.002 · Cited by 461 · see citing works
Impaired adipogenesis and dysfunctional adipose tissue in human hypertrophic obesity
Hammarstedt, A., Gogg, S., Hedjazifar, S., Nerstedt, A., & Smith, U. (2018) · Physiological Reviews · doi:10.1152/physrev.00034.2017 · Cited by 462 · see citing works
Dazert, E., & Hall, M. N. (2011) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2011.09.003 · Cited by 460 · see citing works
Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis
Armstrong, M. J., Hull, D., Guo, K., Barton, D., Hazlehurst, J. M., Gathercole, L. L., Nasiri, M., Yu, J., Gough, S. C., Newsome, P. N., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.08.038 · Cited by 456 · see citing works
From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options
Gastaldelli, A., & Cusi, K. (2019) · JHEP Reports · doi:10.1016/j.jhepr.2019.07.002 · Cited by 455 · see citing works
Taylor, R., Al-Mrabeh, A., Zhyzhneuskaya, S., Peters, C., Barnes, A. C., Aribisala, B. S., Hollingsworth, K. G., Mathers, J. C., Sattar, N., & Lean, M. E. J. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.07.003 · Cited by 450 · see citing works
Insulin signaling in health and disease
Saltiel, A. R. (2021) · Journal of Clinical Investigation · doi:10.1172/jci142241 · Cited by 446 · see citing works
NAFLD as a driver of chronic kidney disease
Byrne, C. D., & Targher, G. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.01.013 · Cited by 449 · see citing works
New insights into the pathophysiology of dyslipidemia in type 2 diabetes
Taskinen, M.-R., & Borén, J. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.01.039 · Cited by 440 · see citing works
Role of Insulin Resistance in MAFLD
Sakurai, Y., Kubota, N., Yamauchi, T., & Kadowaki, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084156 · Cited by 448 · see citing works
Luukkonen, P. K., Sädevirta, S., Zhou, Y., Kayser, B., Ali, A., Ahonen, L., Lallukka, S., Pelloux, V., Gaggini, M., Jian, C., et al. (2018) · Diabetes Care · doi:10.2337/dc18-0071 · Cited by 428 · see citing works
Puri, P., Daita, K., Joyce, A., Mirshahi, F., Santhekadur, P. K., Cazanave, S., Luketic, V. A., Siddiqui, M. S., Boyett, S., Min, H., et al. (2018) · Hepatology · doi:10.1002/hep.29359 · Cited by 426 · see citing works
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 · see citing works
Increased very low density lipoprotein (VLDL) secretion, hepatic steatosis, and insulin resistance
Choi, S. H., & Ginsberg, H. N. (2011) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.04.007 · Cited by 418 · see citing works
Benhamed, F., Denechaud, P.-D., Lemoine, M., Robichon, C., Moldes, M., Bertrand-Michel, J., Ratziu, V., Serfaty, L., Housset, C., Capeau, J., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci41636 · Cited by 408 · see citing works
Svegliati‐Baroni, G., Saccomanno, S., Rychlicki, C., Agostinelli, L., De Minicis, S., Candelaresi, C., Faraci, G., Pacetti, D., Vivarelli, M., Nicolini, D., et al. (2011) · Liver International · doi:10.1111/j.1478-3231.2011.02462.x · Cited by 405 · see citing works
Hong, S.-H., & Choi, K. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020494 · Cited by 390 · see citing works
Azzu, V., Vacca, M., Virtue, S., Allison, M., & Vidal-Puig, A. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.12.054 · Cited by 369 · see citing works
Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH
Caballero, F., Fernández, A., De Lacy, A. M., Fernández-Checa, J. C., Caballería, J., & García-Ruiz, C. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2008.12.016 · Cited by 368 · see citing works
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 · see citing works
Musso, G., Cassader, M., Paschetta, E., & Gambino, R. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.06.031 · Cited by 332 · see citing works
Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration
Sun, Z., Miller, R. A., Patel, R. T., Chen, J., Dhir, R., Wang, H., Zhang, D., Graham, M. J., Unterman, T. G., Shulman, G. I., et al. (2012) · Nature Medicine · doi:10.1038/nm.2744 · Cited by 335 · see citing works
Metabolism of triglyceride-rich lipoproteins in health and dyslipidaemia
Borén, J., Taskinen, M.-R., Björnson, E., & Packard, C. J. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00676-y · Cited by 315 · see citing works
Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans
Pafili, K., & Roden, M. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101122 · Cited by 330 · see citing works
Browning, J. D., Baker, J. A., Rogers, T., Davis, J., Satapati, S., & Burgess, S. C. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.007674 · Cited by 328 · see citing works
Moon, Y.-A., Liang, G., Xie, X., Frank-Kamenetsky, M., Fitzgerald, K., Koteliansky, V., Brown, M. S., Goldstein, J. L., & Horton, J. D. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.017 · Cited by 320 · see citing works
Rector, R. S., Thyfault, J. P., Morris, R. T., Laye, M. J., Borengasser, S. J., Booth, F. W., & Ibdah, J. A. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00428.2007 · Cited by 321 · see citing works
Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors
Francque, S., Szabo, G., Abdelmalek, M. F., Byrne, C. D., Cusi, K., Dufour, J.-F., Roden, M., Sacks, F., & Tacke, F. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00366-5 · Cited by 316 · see citing works
Natural history and progression of metabolic dysfunction-associated steatotic liver disease
Hagström, H., Shang, Y., Hegmar, H., & Nasr, P. (2024) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(24)00193-6 · Cited by 310 · see citing works
Gastaldelli, A., Harrison, S. A., Belfort-Aguilar, R., Hardies, L. J., Balas, B., Schenker, S., & Cusi, K. (2009) · Hepatology · doi:10.1002/hep.23116 · Cited by 285 · see citing works
Dietary carbohydrates and fats in nonalcoholic fatty liver disease
Yki-Järvinen, H., Luukkonen, P. K., Hodson, L., & Moore, J. B. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00472-y · Cited by 294 · see citing works
Bo, T., Gao, L., Yao, Z., Shao, S., Wang, X., Proud, C. G., & Zhao, J. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.04.006 · Cited by 293 · see citing works
Gastrointestinal Complications of Obesity
Camilleri, M., Malhi, H., & Acosta, A. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.12.052 · Cited by 269 · see citing works
Hepatic triacylglycerol accumulation and insulin resistance
Nagle, C. A., Klett, E. L., & Coleman, R. A. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800053-jlr200 · Cited by 272 · see citing works
Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis
Hirsova, P., Ibrabim, S. H., Gores, G. J., & Malhi, H. (2016) · Journal of Lipid Research · doi:10.1194/jlr.r066357 · Cited by 270 · see citing works
Fujita, K., Nozaki, Y., Wada, K., Yoneda, M., Fujimoto, Y., Fujitake, M., Endo, H., Takahashi, H., Inamori, M., Kobayashi, N., et al. (2009) · Hepatology · doi:10.1002/hep.23094 · Cited by 244 · see citing works
Mitochondrial fatty acid oxidation in obesity
Serra, D., Mera, P., Malandrino, M. I., Mir, J. F., & Herrero, L. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4875 · Cited by 246 · see citing works
The Differential Roles of T Cells in Non-alcoholic Fatty Liver Disease and Obesity
Van Herck, M. A., Weyler, J., Kwanten, W. J., Dirinck, E. L., De Winter, B. Y., Francque, S. M., & Vonghia, L. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00082 · Cited by 238 · see citing works
Bates, J., Vijayakumar, A., Ghoshal, S., Marchand, B., Yi, S., Kornyeyev, D., Zagorska, A., Hollenback, D., Walker, K., Liu, K., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.04.037 · Cited by 230 · see citing works
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 · see citing works
Fructose as a key player in the development of fatty liver disease
Basaranoglu, M. (2013) · World Journal of Gastroenterology · doi:10.3748/wjg.v19.i8.1166 · Cited by 235 · see citing works
Chahil, T. J., & Ginsberg, H. N. (2006) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2006.06.002 · Cited by 233 · see citing works
Sweet Sixteenth for ChREBP: Established Roles and Future Goals
Abdul-Wahed, A., Guilmeau, S., & Postic, C. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.004 · Cited by 231 · see citing works
Cuthbertson, D. J., Irwin, A., Gardner, C. J., Daousi, C., Purewal, T., Furlong, N., Goenka, N., Thomas, E. L., Adams, V. L., Pushpakom, S. P., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050117 · Cited by 226 · see citing works
Nonalcoholic fatty liver disease in adults: current concepts in etiology, outcomes, and management
Marjot, T., Moolla, A., Cobbold, J. F., Hodson, L., & Tomlinson, J. W. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnz009 · Cited by 228 · see citing works
ChREBP regulates fructose-induced glucose production independently of insulin signaling
Kim, M.-S., Krawczyk, S. A., Doridot, L., Fowler, A. J., Wang, J. X., Trauger, S. A., Noh, H.-L., Kang, H. J., Meissen, J. K., Blatnik, M., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci81993 · Cited by 212 · see citing works
Lipodystrophy: metabolic insights from a rare disorder
Huang-Doran, I., Sleigh, A., Rochford, J. J., O'Rahilly, S., & Savage, D. B. (2010) · Journal of Endocrinology · doi:10.1677/joe-10-0272 · Cited by 215 · see citing works
Sevastianova, K., Santos, A., Kotronen, A., Hakkarainen, A., Makkonen, J., Silander, K., Peltonen, M., Romeo, S., Lundbom, J., Lundbom, N., et al. (2012) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.038695 · Cited by 211 · see citing works
CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing
Zeng, H., Qin, H., Liao, M., Zheng, E., Luo, X., Xiao, A., Li, Y., Chen, L., Wei, L., Zhao, L., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101428 · Cited by 211 · see citing works
Kotronen, A., Velagapudi, V. R., Yetukuri, L., Westerbacka, J., Bergholm, R., Ekroos, K., Makkonen, J., Taskinen, M.-R., Orešič, M., & Yki-Järvinen, H. (2009) · Diabetologia · doi:10.1007/s00125-009-1282-2 · Cited by 198 · see citing works
Paniagua, J. A. (2016) · World Journal of Diabetes · doi:10.4239/wjd.v7.i19.483 · Cited by 197 · see citing works
Adipose tissue and metabolic syndrome: too much, too little or neither
Grundy, S. M. (2015) · European Journal of Clinical Investigation · doi:10.1111/eci.12519 · Cited by 187 · see citing works
Wada, T., Kenmochi, H., Miyashita, Y., Sasaki, M., Ojima, M., Sasahara, M., Koya, D., Tsuneki, H., & Sasaoka, T. (2010) · Endocrinology · doi:10.1210/en.2009-0869 · Cited by 189 · see citing works
Postprandial metabolism of meal triglyceride in humans
Lambert, J. E., & Parks, E. J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.01.006 · Cited by 182 · see citing works
Self-citation
- Authors
- Donnelly, K. L., Smith, C. I., Schwarzenberg, S. J., Jessurun, J., Boldt, M. D., & Parks, E. J.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Parks, Elizabeth J.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-05-02
- Volume
- 115
- Issue
- 5
- Pages
- 1343-1351
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1087172
- OpenAlex
- W1985592156
- Semantic Scholar
- ed7633369ab77ee37699d391fe0fa59627da0df8
- Cited by
- 3,604
- References
- 50
- Citations by year
- 2026: 158 · 2025: 199 · 2024: 230 · 2023: 268 · 2022: 254 · 2021: 264 · 2020: 229 · 2019: 221 · 2018: 222 · 2017: 184 · 2016: 200 · 2015: 185 · 2014: 163 · 2013: 147 · 2012: 127
- FWCI
- 44.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- University of Minnesota
- National Institutes of Health (RR00400)
- National Institute of Diabetes and Digestive and Kidney Diseases (R03DK058286)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (PAR-98-086)
- National Center for Research Resources (M01RR000400)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- non-alcoholic fatty liver disease, hepatic triglycerides, de novo lipogenesis, free fatty acids, VLDL, stable isotope tracers, fatty acid sources, hepatic lipid accumulation, obesity, hypertriglyceridemia, hyperinsulinemia
- MeSH terms
- Adult, Fatty Acids, Fatty Liver, Female, Humans, Lipoproteins, Liver, Male, Middle Aged, Time Factors, Triglycerides, Cholesterol, VLDL
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
