The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance
Open accessAbstract
Alterations in mitochondrial function have been implicated in the pathogenesis of insulin resistance and type 2 diabetes. However, it is unclear whether the reduced mitochondrial function is a primary or acquired defect in this process. To determine whether primary defects in mitochondrial β-oxidation can cause insulin resistance, we studied mice with a deficiency of long-chain acyl-CoA dehydrogenase (LCAD), a key enzyme in mitochondrial fatty acid oxidation. Here, we show that LCAD knockout mice develop hepatic steatosis, which is associated with hepatic insulin resistance, as reflected by reduced insulin suppression of hepatic glucose production during a hyperinsulinemic-euglycemic clamp. The defects in insulin action were associated with an ≈40% reduction in insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity and an ≈50% decrease in Akt2 activation. These changes were associated with increased PKCε activity and an aberrant 4-fold increase in diacylglycerol content after insulin stimulation. The increase in diacylglycerol concentration was found to be caused by de novo synthesis of diacylglycerol from medium-chain acyl-CoA after insulin stimulation. These data demonstrate that primary defects in mitochondrial fatty acid oxidation capacity can lead to diacylglycerol accumulation, PKCε activation, and hepatic insulin resistance.
Overview
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
Verification
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?
In the citing paper
“Recent studies have shown that increased hepatocellular concentrations of diacylglycerol in nonalcoholic fatty liver disease lead to activation of the protein kinase C epsilon isoform, resulting in reduced insulin signaling and hepatic insulin resistance.23–27”
From Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease (2010) · cites this paper as [27]
In the citing paper
“There is now strong evidence that nonalcoholic fatty liver disease has an important role in causing hepatic insulin resistance.1–3,23–27”
From Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease (2010) · cites this paper as [27]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome
Kadowaki, T. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29126 · Cited by 2,824
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
Self-citationImpaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193
Self-citationMitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107
Self-citationPatti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952
Yu, C., Chen, Y., Cline, G. W., Zhang, D., Zong, H., Wang, Y., Bergeron, R., Kim, J. K., Cushman, S. W., Cooney, G. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200958200 · Cited by 1,561
Self-citationMechanism of hepatic insulin resistance in non-alcoholic fatty liver disease
Samuel, V. T., Liu, Z.-X., Qu, X., Elder, B. D., Bilz, S., Befroy, D., Romanelli, A. J., & Shulman, G. I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313478200 · Cited by 1,322
Self-citationTranscriptional regulatory circuits controlling mitochondrial biogenesis and function
Kelly, D. P., & Scarpulla, R. C. (2004) · Genes & Development · doi:10.1101/gad.1177604 · Cited by 1,243
Holland, W. L., Brozinick, J. T., Wang, L.-P., Hawkins, E. D., Sargent, K. M., Liu, Y., Narra, K., Hoehn, K. L., Knotts, T. A., Siesky, A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.01.002 · Cited by 1,232
Cited by
Sorted by citations
Mechanisms for Insulin Resistance: Common Threads and Missing Links
Samuel, V. T., & Shulman, G. I. (2012) · Cell · doi:10.1016/j.cell.2012.02.017 · Cited by 2,294
Self-citationMyocardial Fatty Acid Metabolism in Health and Disease
Lopaschuk, G. D., Ussher, J. R., Folmes, C. D. L., Jaswal, J. S., & Stanley, W. C. (2010) · Physiological Reviews · doi:10.1152/physrev.00015.2009 · Cited by 2,228
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
Energy Metabolism in the Liver
Rui, L. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130024 · Cited by 2,401
SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., et al. (2010) · Nature · doi:10.1038/nature08778 · Cited by 1,687
Insulin Receptor Signaling in Normal and Insulin-Resistant StatesPreprint
Boucher, J., Kleinridders, A., & Kahn, C. R. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009191 · Cited by 1,550
Lipid-induced insulin resistance: unravelling the mechanism
Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60408-4 · Cited by 1,189
Self-citationThe role of hepatic lipids in hepatic insulin resistance and type 2 diabetes
Perry, R. J., Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2014) · Nature · doi:10.1038/nature13478 · Cited by 1,170
Self-citationEctopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease
Shulman, G. I. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1011035 · Cited by 1,126
Self-citationHirschey, M. D., Shimazu, T., Jing, E., Grueter, C. A., Collins, A. M., Aouizerat, B., Stančáková, A., Goetzman, E., Lam, M. M., Schwer, B., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.07.019 · Cited by 787
“…of the metabolic syndrome, including reduced mass (Kelley et al., 2002), altered morphology (Civitarese et al., 2010), reduced fatty acid oxidation (Zhang et al., 2007), lower oxidative phosphorylation (Befroy et al., 2007; Petersen et al., 2005), and increased Mol reactive oxygen species…”
InfluentialThe 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
Arruda, A. P., Pers, B. M., Parlakgül, G., Güney, E., Inouye, K., & Hotamışlıgil, G. S. (2014) · Nature Medicine · doi:10.1038/nm.3735 · Cited by 741
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
Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment
Golpich, M., Amini, E., Mohamed, Z., Raymond, A. A., Ibrahim, N. M., & Ahmadiani, A. (2016) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12655 · Cited by 555
Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association
Bays, H. E., Toth, P. P., Kris-Etherton, P. M., Abate, N., Aronne, L. J., Brown, W. V., Gonzalez-Campoy, J. M., Jones, S. R., Kumar, R., La Forge, R., et al. (2013) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2013.04.001 · Cited by 521
Treatment of nonalcoholic fatty liver disease: role of AMPK
Smith, B. K., Marcinko, K., Desjardins, E. M., Lally, J., Ford, R. J., & Steinberg, G. R. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00225.2016 · Cited by 509
Diacylglycerol-mediated insulin resistance
Erion, D. M., & Shulman, G. I. (2010) · Nature Medicine · doi:10.1038/nm0410-400 · Cited by 502
Self-citationInsulin resistance in brain alters dopamine turnover and causes behavioral disorders
Kleinridders, A., Cai, W., Cappellucci, L., Ghazarian, A., Collins, W. R., Vienberg, S. G., Pothos, E. N., & Kahn, C. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1500877112 · Cited by 486
Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease
Petersen, K. F., Dufour, S., Hariri, A., Nelson-Williams, C., Foo, J. N., Zhang, X.-M., Dziura, J., Lifton, R. P., & Shulman, G. I. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907295 · Cited by 428
Self-citationMitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis
Pinti, M. V., Fink, G. K., Hathaway, Q. A., Durr, A. J., Kunovac, A., & Hollander, J. M. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00314.2018 · Cited by 447
Ceramide is a cardiotoxin in lipotoxic cardiomyopathy
Park, T., Hu, Y., Noh, H. L., Drosatos, K., Okajima, K., Buchanan, J., Tuinei, J., Homma, S., Jiang, X.-C., Abel, E. D., et al. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800147-jlr200 · Cited by 425
Satapati, S., Sunny, N. E., Kucejova, B., Fu, X., He, T. T., Méndez-Lucas, A., Shelton, J. M., Perales, J. C., Browning, J. D., & Burgess, S. C. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m023382 · Cited by 407
Roles of diacylglycerols and ceramides in hepatic insulin resistance
Petersen, M. C., & Shulman, G. I. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.04.004 · Cited by 373
Self-citationMolecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis
Anderson, N., & Borlak, J. T. (2008) · Pharmacological Reviews · doi:10.1124/pr.108.00001 · Cited by 395
Role of Mitochondria in Nonalcoholic Fatty Liver Disease
Nassir, F., & Ibdah, J. A. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15058713 · Cited by 369
Ussher, J. R., Koves, T. R., Cadete, V. J. J., Zhang, L., Jaswal, J. S., Swyrd, S. J., Lopaschuk, D. G., Proctor, S. D., Keung, W., Muoio, D. M., et al. (2010) · Diabetes · doi:10.2337/db09-1293 · Cited by 381
Diacylglycerol Activation of Protein Kinase Cε and Hepatic Insulin Resistance
Jornayvaz, F. R., & Shulman, G. I. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.005 · Cited by 331
Self-citationWu, S., Lu, Q., Ding, Y., Wu, Y., Qiu, Y., Wang, P., Mao, X., Huang, K., Xie, Z., & Zou, M.-H. (2019) · Circulation · doi:10.1161/circulationaha.118.033552 · Cited by 298
Choi, C. S., Befroy, D. E., Codella, R., Kim, S., Reznick, R. M., Hwang, Y.-J., Liu, Z.-X., Lee, H.-Y., Distefano, A., Samuel, V. T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810339105 · Cited by 279
Self-citationHepatic 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
Mitochondrial Quality Control as a Therapeutic Target
Suliman, H. B., & Piantadosi, C. A. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.011502 · Cited by 267
Glucose Metabolism In Vivo in Four Commonly Used Inbred Mouse Strains
Berglund, E. D., Li, C. Y., Poffenberger, G., Ayala, J. E., Fueger, P. T., Willis, S. E., Jewell, M. M., Powers, A. C., & Wasserman, D. H. (2008) · Diabetes · doi:10.2337/db07-1615 · Cited by 265
BNip3 Regulates Mitochondrial Function and Lipid Metabolism in the Liver
Glick, D., Zhang, W., Beaton, M., Marsboom, G., Gruber, M., Simon, M. C., Hart, J., Dorn, G. W., Brady, M. J., & Macleod, K. F. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00167-12 · Cited by 251
Non-Alcoholic Fatty Liver Disease
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_19 · Cited by 253
Qatanani, M., Szwergold, N. R., Greaves, D. R., Ahima, R. S., & Lazar, M. A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37273 · Cited by 230
Santoro, N., Kursawe, R., D’Adamo, E., Dykas, D. J., Zhang, C. K., Bale, A. E., Cali, A. M. G., Narayan, D., Shaw, M. M., Pierpont, B. M., et al. (2010) · Hepatology · doi:10.1002/hep.23832 · Cited by 219
Self-citationRole of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes
Zorzano, A., Liesa, M., & Palacín, M. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.02.004 · Cited by 209
Nagai, Y., Yonemitsu, S., Erion, D. M., Iwasaki, T., Stark, R., Weismann, D., Dong, J., Zhang, D., Jurczak, M. J., Löffler, M. G., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.01.011 · Cited by 203
Self-citationLiu, Y., Wang, J., WEI, Y., Zhang, H., XU, M., & DAI, J. (2008) · Aquatic Toxicology · doi:10.1016/j.aquatox.2008.07.009 · Cited by 192
Hepatic Steatosis as a Marker of Metabolic Dysfunction
Fabbrini, E., & Magkos, F. (2015) · Nutrients · doi:10.3390/nu7064995 · Cited by 192
SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism
Hirschey, M. D., Shimazu, T., Huang, J. Y., Schwer, B., & Verdin, E. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010850 · Cited by 180
Stimulation of glucose oxidation protects against acute myocardial infarction and reperfusion injury
Ussher, J. R., Wang, W., Gandhi, M., Keung, W., Samokhvalov, V., Oka, T., Wagg, C. S., Jaswal, J. S., Harris, R. A., Clanachan, A. S., et al. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs129 · Cited by 184
Wang, X., Liu, R., Zhang, W., Zhang, X., Liao, N., Wang, Z., Li, W., Qin, X., & Hai, C. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.06.014 · Cited by 172
Wang, C., Wang, C., Huang, H., & Wei, Y. (2013) · The FEBS Journal · doi:10.1111/febs.12096 · Cited by 165
Hokayem, M., Blond, E., Vidal, H., Lambert, K., Meugnier, E., Feillet‐Coudray, C., Coudray, C., Pesenti, S., Luyton, C., Lambert-Porcheron, S., et al. (2012) · Diabetes Care · doi:10.2337/dc12-1652 · Cited by 170
Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity
Patterson, R. E., Kalavalapalli, S., Williams, C. M., Nautiyal, M., Mathew, J. T., Martinez, J., Reinhard, M. K., McDougall, D. J., Rocca, J. R., Yost, R. A., et al. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00492.2015 · Cited by 161
Mitochondrial Roles and Cytoprotection in Chronic Liver Injury
Esposti, D. D., Hamelin, J., Bosselut, N., Saffroy, R., Sebagh, M., Pommier, A., Martel, C., & Lemoine, A. (2012) · Biochemistry Research International · doi:10.1155/2012/387626 · Cited by 165
Son, N.-H., Yu, S., Tuinei, J., Arai, K., Hamai, H., Homma, S., Shulman, G. I., Abel, E. D., & Goldberg, I. J. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40905 · Cited by 159
Self-citationInsulin Resistance and Mitochondrial Dysfunction
González-Franquesa, A., & Patti, M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-55330-6_25 · Cited by 160
Estall, J. L., Kahn, M., Cooper, M. P., Fisher, F. M., Wu, M. K., Laznik, D., Qu, L., Cohen, D. E., Shulman, G. I., & Spiegelman, B. M. (2009) · Diabetes · doi:10.2337/db08-1571 · Cited by 149
Self-citationAharoni-Simon, M., Hahn-Obercyger, M., Pen, S., Madar, Z., & Tirosh, O. (2011) · Laboratory Investigation · doi:10.1038/labinvest.2011.55 · Cited by 143
Jurczak, M. J., Lee, A., Jornayvaz, F. R., Lee, H., Birkenfeld, A. L., Guigni, B. A., Kahn, M., Samuel, V. T., Glimcher, L. H., & Shulman, G. I. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.316760 · Cited by 143
Self-citationGenetic determinants of hepatic steatosis in man
Hooper, A. J., Adams, L. A., & Burnett, J. R. (2011) · Journal of Lipid Research · doi:10.1194/jlr.r008896 · Cited by 149
Sirtuins and Insulin Resistance
Zhou, S., Tang, X., & Chen, H. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00748 · Cited by 155
He, K., Hu, Y., Ma, H., Zou, Z., Xiao, Y., Yang, Y., Feng, M., Li, X., & Ye, X. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.06.006 · Cited by 140
Ussher, J. R., Koves, T. R., Jaswal, J. S., Zhang, L., Ilkayeva, O., Dyck, J. R. B., Muoio, D. M., & Lopaschuk, G. D. (2009) · Diabetes · doi:10.2337/db09-0011 · Cited by 135
The Role of Lipid and Lipoprotein Metabolism in Non‐Alcoholic Fatty Liver Disease
Perla, F. M., Prelati, M., Lavorato, M., Visicchio, D., & Anania, C. (2017) · Children · doi:10.3390/children4060046 · Cited by 144
Hepatic Fatty Acid Oxidation Restrains Systemic Catabolism during Starvation
Lee, J., Choi, J., Scafidi, S., & Wolfgang, M. J. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.062 · Cited by 131
Wang, C., Ching-chū, W., & Wei, Y. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05625.x · Cited by 120
A Role of the Bile Salt Receptor FXR in Atherosclerosis
Hageman, J., Herrema, H., Groen, A. K., & Kuipers, F. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.197897 · Cited by 122
Mechanistic review of drug-induced steatohepatitis
Schumacher, J. D., & Guo, G. L. (2015) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2015.08.022 · Cited by 113
Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis
Hiramitsu, M., Shimada, Y., Kuroyanagi, J., Inoue, T., Katagiri, T., Zang, L., Nishimura, Y., Nishimura, N., & Tanaka, T. (2014) · Scientific Reports · doi:10.1038/srep03708 · Cited by 114
Compartmentalized Acyl-CoA Metabolism in Skeletal Muscle Regulates Systemic Glucose Homeostasis
Li, L. O., Grevengoed, T. J., Paul, D. S., Ilkayeva, O., Koves, T. R., Pascual, F. L., Newgard, C. B., Muoio, D. M., & Coleman, R. (2014) · Diabetes · doi:10.2337/db13-1070 · Cited by 107
Legaki, A., Moustakas, I. I., Sikorska, M., Papadopoulos, G., Velliou, R.-I., & Chatzigeorgiou, A. (2022) · Current Obesity Reports · doi:10.1007/s13679-022-00473-1 · Cited by 111
Kursawe, R., Caprio, S., Giannini, C., Narayan, D., Lin, A., D’Adamo, E., Shaw, M. M., Pierpont, B. M., Cushman, S. W., & Shulman, G. I. (2012) · Diabetes · doi:10.2337/db12-0889 · Cited by 109
Self-citationObesogenic high fat western diet induces oxidative stress and apoptosis in rat heart
Ballal, K., Wilson, C. R., Harmancey, R., & Taegtmeyer, H. (2010) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-010-0546-y · Cited by 100
Civitarese, A. E., MacLean, P. S., Carling, S., Kerr-Bayles, L., McMillan, R. P., Pierce, A., Becker, T. C., Moro, C., Finlayson, J., Lefort, N., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.04.004 · Cited by 95
The malonyl CoA axis as a potential target for treating ischaemic heart disease
Ussher, J. R., & Lopaschuk, G. D. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn130 · Cited by 94
Hafizi Abu Bakar, M., Kian Kai, C., Wan Hassan, W. N., Sarmidi, M. R., Yaakob, H., & Zaman Huri, H. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2601 · Cited by 91
Lee, J., Choi, J., Alpergin, E. S. S., Zhao, L., Härtung, T., Scafidi, S., Riddle, R. C., & Wolfgang, M. J. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.06.080 · Cited by 92
ACADL plays a tumor-suppressor role by targeting Hippo/YAP signaling in hepatocellular carcinoma
Zhao, X., Qin, W., Jiang, Y., Yang, Z., Yuan, B., Dai, R., Shen, H., Chen, Y., Fu, J., & Wang, H. (2020) · npj Precision Oncology · doi:10.1038/s41698-020-0111-4 · Cited by 86
Functional proteomic analysis of nonalcoholic fatty liver disease in rat models
Zhang, X., Yang, J., Guo, Y., Ye, H., Yu, C., Xu, C., Xu, L., Wu, S., Sun, W., Wei, H., et al. (2009) · Hepatology · doi:10.1002/hep.23486 · Cited by 85
Zhang, D., Christianson, J., Liu, Z., Tian, L., Choi, C. S., Neschen, S., Dong, J., Wood, P. A., & Shulman, G. I. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.012 · Cited by 84
Self-citationProgressive adaptation of hepatic ketogenesis in mice fed a high-fat diet
Sunny, N. E., Satapati, S., Fu, X., He, T., Mehdibeigi, R., Spring-Robinson, C. L., Duarte, J. A. G., Potthoff, M. J., Browning, J. D., & Burgess, S. C. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00033.2010 · Cited by 85
Advances in the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease
Yin, X., Guo, X., Liu, Z., & Wang, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032844 · Cited by 86
Self-citationFeyter, H. M. D., Lenaers, E., Houten, S. M., Schrauwen, P., Hesselink, M. K. C., Wanders, R. J. A., Nicolay, K., & Prompers, J. J. (2008) · The FASEB Journal · doi:10.1096/fj.08-112318 · Cited by 79
Physiological Suppression of Lipotoxic Liver Damage by Complementary Actions of HDAC3 and SCAP/SREBP
Papazyan, R., Sun, Z., Kim, Y. H., Titchenell, P. M., Hill, D. A., Lu, W., Damle, M., Wan, M., Zhang, Y., Briggs, E. R., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.10.012 · Cited by 80
Goedeke, L., Perry, R. J., & Shulman, G. I. (2019) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104727 · Cited by 76
Self-citationPathophysiology of NASH in endocrine diseases
Gariani, K., & Jornayvaz, F. R. (2021) · Endocrine Connections · doi:10.1530/ec-20-0490 · Cited by 77
Diabetes and Alzheimer’s Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?
Potenza, M. A., Sgarra, L., Desantis, V., Nacci, C., & Montagnani, M. (2021) · Antioxidants · doi:10.3390/antiox10081257 · Cited by 78
Protein Carbonylation in a Murine Model for Early Alcoholic Liver Disease
Galligan, J. J., Smathers, R. L., Fritz, K. S., Epperson, L. E., Hunter, L. E., & Petersen, D. R. (2012) · Chemical Research in Toxicology · doi:10.1021/tx300002q · Cited by 74
Lustgarten, M. S., Price, L. L., Phillips, E. M., & Fielding, R. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084034 · Cited by 74
Kim, S.-J., Chae, S., Kim, H., Mun, D., Back, S., Choi, H. Y., Park, K. S., Hwang, D., Choi, S. H., & Lee, S. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.035501 · Cited by 72
Minireview: Mitochondrial Energetics and Insulin Resistance
Civitarese, A. E., & Ravussin, E. (2008) · Endocrinology · doi:10.1210/en.2007-1444 · Cited by 70
Rieusset, J. (2015) · Diabetes & Metabolism · doi:10.1016/j.diabet.2015.02.006 · Cited by 69
Ussher, J. R., & Lopaschuk, G. D. (2009) · Basic Research in Cardiology · doi:10.1007/s00395-009-0003-9 · Cited by 68
Rector, R. S., Morris, E. M., Ridenhour, S. E., Meers, G. M.-E., Hsu, F., TURK, J. W., & Ibdah, J. A. (2013) · Hepatology · doi:10.1002/hep.26285 · Cited by 69
Zhou, J. Y., Poudel, A., Welchko, R. M., Mekala, N. K., Chandramani-Shivalingappa, P., Rosca, M. G., & Li, L. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.172594 · Cited by 73
Henkel, J., Frede, K., Schanze, N., Vogel, H., Schürmann, A., Spruss, A., Bergheim, I., & Püschel, G. P. (2012) · Laboratory Investigation · doi:10.1038/labinvest.2012.128 · Cited by 68
Antonio Zorzano, A., Hernández‐Álvarez, M. I., Palacín, M., & Mingrone, G. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.02.017 · Cited by 69
Mechanism by which arylamine N -acetyltransferase 1 ablation causes insulin resistance in mice
Camporez, J. P., Wang, Y., Faarkrog, K., Chukijrungroat, N., Petersen, K. F., & Shulman, G. I. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716990115 · Cited by 67
Self-citationMoon, S. H., Jenkins, C. M., Liu, X., Guan, S., Mancuso, D. J., & Gross, R. W. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.336776 · Cited by 65
Gao, X., Chen, W., Kong, X., Xu, A., Wang, Z. G., Sweeney, G., & Wu, D. (2009) · Diabetologia · doi:10.1007/s00125-009-1284-0 · Cited by 69
Changes in Cells Associated with Insulin Resistance
Szablewski, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042397 · Cited by 78
Leem, J., & Koh, E. H. (2011) · Experimental Diabetes Research · doi:10.1155/2012/242984 · Cited by 62
Zamora-Mendoza, R. G., Rosas‐Vargas, H., Ramos-Cervantes, M. T., García-Zúñiga, P. A., Pérez-Lorenzana, H., Mendoza‐Lorenzo, P., Perez-Ortiz, A. C., Estrada-Mena, F. J., Miliar-García, Á., Lara‐Padilla, E., et al. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.274 · Cited by 62
Warren, B. E., Lou, P., Lucchinetti, E., Zhang, L., Clanachan, A. S., Affolter, A., Hersberger, M., Zaugg, M., & Lemieux, H. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00511.2013 · Cited by 56
Zhao, L., Zhong, S., Qu, H., Xie, Y., Cao, Z., Li, Q., Yang, P., Varghese, Z., Moorhead, J. F., Chen, Y., et al. (2015) · Scientific Reports · doi:10.1038/srep10222 · Cited by 57
Amrutkar, M., Kern, M., Nuñez‐Durán, E., Ståhlman, M., Cansby, E., Chursa, U., Stenfeldt, E., Borén, J., Blüher, M., & Mahlapuu, M. (2015) · Diabetologia · doi:10.1007/s00125-015-3801-7 · Cited by 57
Wen, F., An, C., Wu, X., Yang, Y., Xu, J., Liu, Y., Wang, C., Nie, L., Fang, H., & Yang, Z. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.11.008 · Cited by 57
Metadata
- Authors
- Zhang, D., Liu, Z.-X., Choi, C. S., Tian, L., Kibbey, R., Dong, J., Cline, G. W., Wood, P. A., & Shulman, G. I.
- Affiliations
- Howard Hughes Medical Institute (US)
- *Howard Hughes Medical Institute and
- Departments of †Internal Medicine and
- University of Alabama at Birmingham (US)
- Corresponding author
- Shulman, Gerald I.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-10-23
- Volume
- 104
- Issue
- 43
- Pages
- 17075-17080
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2040460
- OpenAlex
- W2091450162
- Cited by
- 291
- References
- 27
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 10 · 2023: 22 · 2022: 14 · 2021: 11 · 2020: 9 · 2019: 14 · 2018: 13 · 2017: 19 · 2016: 15 · 2015: 19 · 2014: 25 · 2013: 15 · 2012: 22
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- U.S. Public Health Service (R01 DK-40936)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK40936, U24DK59635, R01DK040936, U24DK059635)
- National Center for Research Resources (R01-RR02599, R01RR002599)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- long-chain acyl-CoA dehydrogenase deficiency, mitochondrial dysfunction, hepatic steatosis, hepatic insulin resistance, mitochondrial fatty acid oxidation, insulin receptor substrate 2, phosphatidylinositol 3-kinase, AKT2, protein kinase C epsilon, diacylglycerol, type 2 diabetes
- MeSH terms
- Acyl Coenzyme A, Animals, Calorimetry, Carbon Isotopes, Diglycerides, Energy Metabolism, Fatty Liver, Gene Expression Regulation, Glucose, Homeostasis, Insulin, Insulin Resistance, Liver, Mitochondria, Oxidation-Reduction, Triglycerides, Signal Transduction, Muscle, Skeletal, Acyl-CoA Dehydrogenase, Long-Chain, Mice, Protein Kinase C-epsilon
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
