Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice

Neschen, Susanne; Morino, Katsutaro; Hammond, Linda E.; Zhang, Dongyan; Liu, Zhen-Xiang; Romanelli, Anthony J.; Cline, Gary W.; Pongratz, Rebecca L.; Zhang, Xian-Man; Choi, Cheol S.; Coleman, Rosalind A.; Shulman, Gerald I.

doi:10.1016/j.cmet.2005.06.006

Cited by 261Liver Disease Diagnosis and TreatmentLipid metabolism and biosynthesisDiet, Metabolism, and Disease

Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice

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Neschen, Susanne, Morino, Katsutaro, Hammond, Linda E., Zhang, Dongyan, Liu, Zhen-Xiang, Romanelli, Anthony J., Cline, Gary W., Pongratz, Rebecca L. +4 more·2005·Cell Metabolism

DOI 10.1016/j.cmet.2005.06.006

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Abstract

In order to investigate the role of mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 (mtGPAT1) in the pathogenesis of hepatic steatosis and hepatic insulin resistance, we examined whole-body insulin action in awake mtGPAT1 knockout (mtGPAT1(-/-)) and wild-type (wt) mice after regular control diet or three weeks of high-fat feeding. In contrast to high-fat-fed wt mice, mtGPAT1(-/-) mice displayed markedly lower hepatic triacylglycerol and diacylglycerol concentrations and were protected from hepatic insulin resistance possibly due to a lower diacylglycerol-mediated PKC activation. Hepatic acyl-CoA has previously been implicated in the pathogenesis of insulin resistance. Surprisingly, compared to wt mice, mtGPAT1(-/-) mice exhibited increased hepatic insulin sensitivity despite an almost 2-fold elevation in hepatic acyl-CoA content. These data suggest that mtGPAT1 might serve as a novel target for treatment of hepatic steatosis and hepatic insulin resistance and that long chain acyl-CoA's do not mediate fat-induced hepatic insulin resistance in this model.

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NAFLD-induced hepatic insulin resistance is a major factor responsible for the transition from normoglycemia to fasting hyperglycemia and T2DM.
“recent studies have demonstrated that NAFLD-induced hepatic insulin resistance is a major factor responsible for the transition from normoglycemia to fasting hyperglycemia and T2DM (18–23).”
From The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome (2007) · cites this paper as [22]
NAFLD is strongly linked to hepatic insulin resistance.
“NAFLD is strongly linked to hepatic insulin resistance”
From The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome (2007) · cites this paper as [22]
In this setting, PKCε, but not other isoforms of PKC, is activated.
“In this setting, PKCε, but not other isoforms of PKC, is activated.”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
Hepatic steatosis per se causes hepatic insulin resistance.
“An alternate hypothesis is that the development of hepatic steatosis per se causes hepatic insulin resistance.”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
Preventing fat accumulation in rodents preserves hepatic insulin action.
“Preventing fat accumulation in rodents preserves hepatic insulin action (7,10,12).”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]

Preventing fat accumulation by inhibiting lipid synthesis via disruption of mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase or promoting fat oxidation using either mitochondrial uncoupler 2,4-dinitrophenol or inhibition of acetyl-CoA carboxylase-1 and -2 prevents PKCε activation and hepatic insulin resistance.
“Preventing fat accumulation by inhibiting lipid synthesis via disruption of the mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase (7) or promoting fat oxidation using either the mitochondrial uncoupler 2,4-dinitrophenol (10) or inhibition of acetyl-CoA carboxylase-1 and -2 (12) prevents PKCε activation and hepatic insulin resistance.”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
DAG is a known activator of classic and novel isoforms of PKC.
“This is important since DAG is a known activator of classic and novel isoforms of PKC and DAG concentrations have closely paralleled insulin resistance in other models (7,12).”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
DAG concentrations have closely paralleled insulin resistance in other models.
“This is important since DAG is a known activator of classic and novel isoforms of PKC and DAG concentrations have closely paralleled insulin resistance in other models (7,12).”
From Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease (2007) · cites this paper as [7]
There is increasing evidence for a causal relationship between hepatic steatosis and hepatic insulin resistance in rodent models and in patients with nonalcoholic fatty liver disease.
“There is increasing evidence for a causal relationship between hepatic steatosis and hepatic insulin resistance both in rodent models with hepatic steatosis and in patients with nonalcoholic fatty liver disease (4, 18-25).”
From Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men (2006) · cites this paper as [22]

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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 · see citing works
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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 · see citing works
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Perseghin, G., Scifo, P., De Cobelli, F., Pagliato, E., Battezzati, A., Arcelloni, C., Vanzulli, A., Testolin, G., Pozza, G., Del Maschio, A., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.8.1600 · Cited by 877 · see citing works
Unsaturated diacylglycerol as a possible messenger for the activation of calcium-activated, phospholipid-dependent protein kinase system
Takai, Y., Kishimoto, A., Kikkawa, U., Terutoshi, M. O. R. I., & Nishizuka, Y. (1979) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(79)91197-5 · Cited by 731 · see citing works
The Effects of Rosiglitazone on Insulin Sensitivity, Lipolysis, and Hepatic and Skeletal Muscle Triglyceride Content in Patients With Type 2 Diabetes
Mayerson, A. B., Hundal, R. S., Dufour, S., Lebon, V., Befroy, D., Cline, G. W., Enocksson, S., Inzucchi, S. E., Shulman, G. I., & Petersen, K. F. (2002) · Diabetes · doi:10.2337/diabetes.51.3.797 · Cited by 647 · see citing works
Self-citation
Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase‐1 and p70 S6 kinase
Alessi, D. R., Barry Caudwell, F., Andjelkovic, M., Hemmings, B. A., & Cohen, P. (1996) · FEBS Letters · doi:10.1016/s0014-5793(96)01370-1 · Cited by 628 · see citing works
Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy
Petersen (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215001 · Cited by 622 · cited 1× · see citing works
“Furthermore recent studies have demonstrated an important role of hepatic steatosis in the pathogenesis of hepatic insulin resistance, increased hepatic gluconeogenesis, and fasting hyperglycemia in patients with type 2 diabetes (Mayerson et al., 2002, Petersen et al., 2005; Petersen et al., 2002; Pietilainen et al.,…”
BackgroundSelf-citation
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Stone, S. J., Myers, H. M., Watkins, S. M., Brown, B. E., Feingold, K. R., Elias, P. M., & Farese, R. V. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311000200 · Cited by 600 · 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
Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver
Dobrzyń, P., Dobrzyń, A., Miyazaki, M., Cohen, P., Asilmaz, E., Hardie, D. G., Friedman, J. M., & Ntambi, J. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401627101 · Cited by 393 · see citing works
Decreased Plasma Adiponectin Concentrations Are Closely Related to Hepatic Fat Content and Hepatic Insulin Resistance in Pioglitazone-Treated Type 2 Diabetic Patients
Bajaj, M. S., Suraamornkul, S., Piper, P. K., Hardies, L. J., Glass, L. C., Cersósimo, E., Pratipanawatr, T., Miyazaki, Y., & DeFronzo, R. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031315 · Cited by 354 · see citing works
Physiological and Nutritional Regulation of Enzymes of Triacylglycerol Synthesis
Coleman, R., Lewin, T. M., & Muoio, D. M. (2000) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.20.1.77 · Cited by 352 · see citing works
Self-citation
Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1
Chen, H. C., Smith, S. J., Ladha, Z., Jensen, D. R., Ferreira, L. D., Pulawa, L. K., McGuire, J. G., Pitas, R. E., Eckel, R. H., & Farese, R. V. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14672 · Cited by 329 · see citing works
PPAR-RXR Heterodimer Activates a Peroxisome Proliferator Response Element Upstream of the Bifunctional Enzyme Gene
Bardot, O., Aldridge, T. C., Latruffe, N., & Green, S. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1378 · Cited by 269 · see citing works
The role of intramuscular lipid in insulin resistance
Hegarty, B. D., Furler, S. M., Ye, J.-M., Cooney, G. J., & Kraegen, E. W. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01162.x · Cited by 256 · see citing works
Insulin stimulation of phosphatidylinositol 3-kinase activity and association with insulin receptor substrate 1 in liver and muscle of the intact rat.
Folli, F. B., Saad, M. J. A., Backer, J., & Kahn, C. R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41650-x · Cited by 254 · see citing works
Peroxisomal and Mitochondrial Fatty Acid β-Oxidation in Mice Nullizygous for Both Peroxisome Proliferator-activated Receptor α and Peroxisomal Fatty Acyl-CoA Oxidase
Hashimoto, T., Fujita, T., Usuda, N., Cook, W., Qi, C., Peters, J. M., Gonzalez, F. J., Yeldandi, A. V., Rao, M. S., & Reddy, J. K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.27.19228 · Cited by 241 · see citing works
Cloning and expression of mouse fatty acid synthase and other specific mRNAs. Developmental and hormonal regulation in 3T3-L1 cells.
Paulauskis, J. D., & Sul, H. S. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68602-8 · Cited by 204 · see citing works
Mitochondrial Glycerol-3-Phosphate Acyltransferase-Deficient Mice Have Reduced Weight and Liver Triacylglycerol Content and Altered Glycerolipid Fatty Acid Composition
Hammond, L. E., Gallagher, P. A., Wang, S., Hiller, S., Kluckman, K. D., Posey-Marcos, E. L., Maeda, N., & Coleman, R. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.23.8204-8214.2002 · Cited by 198 · see citing works
Self-citation
Two -acting regulatory sequences in the peroxisome proliferator-responsive enhancer region of rat acyl-CoA oxidase gene
Osumi, T., Wen, J., & Hashimoto, T. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91645-s · Cited by 197 · see citing works
WY14,643, a Peroxisome Proliferator-activated Receptor α (PPARα) Agonist, Improves Hepatic and Muscle Steatosis and Reverses Insulin Resistance in Lipoatrophic A-ZIP/F-1 Mice
Chou, C. J., Haluzı́k, M., Gregory, C., Dietz, K. R., Vinson, C., Gavrilova, O., & Reitman, M. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202449200 · Cited by 197 · see citing works
Convergence of Multiple Signaling Cascades at Glycogen Synthase Kinase 3: Edg Receptor-Mediated Phosphorylation and Inactivation by Lysophosphatidic Acid through a Protein Kinase C-Dependent Intracellular Pathway
Fang, X., Yu, S., Tanyi, J. L., Lu, Y., Woodgett, J. R., & Mills, G. B. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.2099-2110.2002 · Cited by 174 · see citing works
Skeletal muscle triacylglycerol in the rat: methods for sampling and measurement, and studies of biological variability.
Frayn, K. N., & Maycock, P. F. (1980) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39849-7 · Cited by 173 · see citing works
Overexpression of Glut4 protein in muscle increases basal and insulin-stimulated whole body glucose disposal in conscious mice.
Ren, J., Marshall, B. A., Mueckler, M. M., McCaleb, M. L., Amatruda, J. M., & Shulman, G. I. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117673 · Cited by 171 · see citing works
Self-citation
Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content
Neschen, S., Moore, I. K., Regittnig, W., Yu, C. L., Wang, Y., Pypaert, M., Petersen, K. F., & Shulman, G. I. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00414.2001 · Cited by 155 · see citing works
Self-citation
Protein kinase C is increased in the liver of humans and rats with non-insulin-dependent diabetes mellitus: an alteration not due to hyperglycemia.
Considine, R. V., Nyce, M. R., Allen, L. E., Morales, L. M., Triester, S., Serrano, J., Colberg, J., Lanza-Jacoby, S., & Caro, J. F. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118001 · Cited by 141 · see citing works
A Substrate- and Position-specific Acylation of sn-Glycerol 3-Phosphate by Rat Liver Mitochondria
Monroy, G. C., Rola, F. H., & Pullman, M. E. (1972) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)44668-1 · Cited by 134 · see citing works
Rat peroxisomal 3-ketoacyl-CoA thiolase gene. Occurrence of two closely related but differentially regulated genes.
Hijikata, M., Wen, J., Osumi, T., & Hashimoto, T. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39605-x · Cited by 130 · see citing works
The role of lipids in the pathogenesis of muscle insulin resistance and beta cell failure in type II diabetes and obesity
Kraegen, E. W., Cooney, G. J., Ye, J.-M., Thompson, A., & Furler, S. M. (2001) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2001-18581 · Cited by 130 · see citing works
Tissue and isoform-selective activation of protein kinase C in insulin-resistant obese Zucker rats - effects of feeding.
Qu, X.-Q., Seale, J., & Donnelly, R. (1999) · Journal of Endocrinology · doi:10.1677/joe.0.1620207 · Cited by 123 · see citing works
Isolation and Quantitation of Long-Chain Acyl-Coenzyme A Esters in Brain Tissue by Solid-Phase Extraction
Deutsch, J., Grange, E., Рапопорт, С. И., & Purdon, A. D. (1994) · Analytical Biochemistry · doi:10.1006/abio.1994.1344 · Cited by 119 · see citing works
Increased Hepatic Insulin Sensitivity Together with Decreased Hepatic Triglyceride Stores in Hormone-Sensitive Lipase-Deficient Mice
Voshol, P. J., Haemmerle, G., Ouwens, D. M., Zimmermann, R., Zechner, R., Teusink, B., Maassen, J. A., Havekes, L. M., & Romijn, J. A. (2003) · Endocrinology · doi:10.1210/en.2002-0036 · Cited by 119 · see citing works
Differential effects of safflower oil versus fish oil feeding on insulin-stimulated glycogen synthesis, glycolysis, and pyruvate dehydrogenase flux in skeletal muscle: a 13C nuclear magnetic resonance study.
Jucker, B. M., Cline, G. W., Barucci, N., & Shulman, G. I. (1999) · Diabetes · doi:10.2337/diabetes.48.1.134 · Cited by 119 · see citing works
Self-citation
A novel, noninvasive method for the measurement of intestinal fat absorption
Jandacek, R. J., Heubi, J. E., & Tso, P. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.04.007 · Cited by 117 · see citing works
Identification of a New Glycerol-3-phosphate Acyltransferase Isoenzyme, mtGPAT2, in Mitochondria
Lewin, T. M., Schwerbrock, N. M. J., Lee, D. P., & Coleman, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314032200 · Cited by 111 · see citing works
Self-citation
Overexpression of mitochondrial GPAT in rat hepatocytes leads to decreased fatty acid oxidation and increased glycerolipid biosynthesis
Lindén, D., William‐Olsson, L., Rhedin, M., Asztély, A.-K., Clapham, J. C., & Schreyer, S. A. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m400010-jlr200 · Cited by 107 · see citing works
Transcriptional regulation of p90 with sequence homology to Escherichia coli glycerol-3-phosphate acyltransferase.
Shin, D. H., Paulauskis, J. D., Moustaïd, N., & Sul, H. S. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54359-3 · Cited by 97 · see citing works
Mitochondrial Glycerol Phosphate Acyltransferase Directs the Incorporation of Exogenous Fatty Acids into Triacylglycerol
Igal, R. A., Wang, S., González-Baró, M. R., & Coleman, R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103386200 · Cited by 97 · see citing works
Self-citation
Cellular Mechanism of Nutritionally Induced Insulin Resistance in Psammomys Obesus
Ikeda, Y., Olsen, G. S., Ziv, E., Hansen, L. L., Busch, A. K., Hansen, B. F., Shafrir, E., & Mosthaf, L. (2001) · Diabetes · doi:10.2337/diabetes.50.3.584 · Cited by 93 · see citing works
Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins
Pietiläinen, K. H., Rissanen, A., Kaprio, J. A., Mäkimattila, S., Häkkinen, A., Westerbacka, J., Sutinen, J., Vehkavaara, S., & Yki‐Järvinen, H. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00381.2004 · Cited by 90 · see citing works
Expression and identification of p90 as the murine mitochondrial glycerol-3-phosphate acyltransferase
Yet, S., Lee, S.-J., Hahm, Y. T., & Sul, H. S. (1993) · Biochemistry · doi:10.1021/bi00087a029 · Cited by 88 · see citing works
Effects of high fat-feeding to rats on the interrelationship of body weight, plasma insulin, and fatty acyl-coenzyme a esters in liver and skeletal muscle
Chen, M.-T., Kaufman, L. N., Spennetta, T., & Shrago, E. (1992) · Metabolism · doi:10.1016/0026-0495(92)90221-u · Cited by 83 · see citing works
Expression of the major isoenzyme of protein kinase-C in skeletal muscle, nPKC theta, varies with muscle type and in response to fructose- induced insulin resistance
Donnelly, R., Reed, M. J., Azhar, S., & Reaven, G. M. (1994) · Endocrinology · doi:10.1210/endo.135.6.7988419 · Cited by 82 · see citing works
Regulation of Mitochondrial sn-Glycerol-3-phosphate Acyltransferase Activity: Response to Feeding Status Is Unique in Various Rat Tissues and Is Discordant with Protein Expression
Lewin, T. M., Granger, D. A., Kim, J. H., & Coleman, R. (2001) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2001.2604 · Cited by 76 · see citing works
Self-citation
Adrenalectomy reverses insulin resistance in muscle from obese (ob/ob) mice
Ohshima, K., Shargill, N. S., Chan, T. M., & Bray, G. A. (1984) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1984.246.2.e193 · Cited by 60 · see citing works
Mitochondrial glycerol-3-phosphate acyltransferase-1 directs the metabolic fate of exogenous fatty acids in hepatocytes
Lewin, T. M., Wang, S., Nagle, C. A., Horn, C. G. V., & Coleman, R. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00300.2004 · Cited by 59 · see citing works
Self-citation
Induction of cytochrome p450 and peroxisomal enzymes by clofibric acid in vivo and in VITRO
Bars, R., Bell, D., & Elcombe, C. R. (1993) · Biochemical Pharmacology · doi:10.1016/0006-2952(93)90015-o · Cited by 53 · see citing works
Rat sn-glycerol-3-phosphate acyltransferase: molecular cloning and characterization of the cDNA and expressed protein
Bhat, B. G., WANG, P. H., Kim, J. H., Black, T. M., Lewin, T. M., Fiedorek, F. T., & Coleman, R. (1999) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(99)00103-1 · Cited by 53 · see citing works
Self-citation
Discovery and Prospect of Protein Kinase C Research: Epilogue
Nishizuka, Y. (2003) · The Journal of Biochemistry · doi:10.1093/jb/mvg035 · Cited by 49 · see citing works
Transcriptional induction of the fatty acid binding protein gene in mouse liver by bezafibrate
Besnard, P., Mallordy, A., & CARLIER, H. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)80173-r · Cited by 46 · see citing works
Differentiation of microsomal from lysosomal triacylglycerol lipase activities in rat liver
Coleman, R., & Haynes, E. B. (1983) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(83)90177-7 · Cited by 34 · see citing works
Self-citation
Determination of the molecular species composition of diacylglycerols in human adipose tissue by solid-phase extraction and gas chromatography on a polar phase
Pacheco, Y. M., del Camino, M., Cert, A., Montero, E., & Ruíz-Gutiérrez, V. (1998) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(98)00231-x · Cited by 17 · see citing works
Prostaglandylinositol cyclic phosphate (cPIP): a novel second messenger of insulin action. Comparative analysis of two kinds of ‘insulin mediators’
Shashkin, P. N., Wasner, H. K., Ortmeyer, H. K., & HANSEN, B. C. (2001) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.218 · Cited by 12 · see citing works

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Self-citation
Obesity-associated improvements in metabolic profile through expansion of adipose tissue
Kim, J.-Y., van de Wall, E., Laplante, M., Azzara, A., Trujillo, M. E., Hofmann, S. M., Schraw, T., Durand, J. L., Li, H., Li, G., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31021 · Cited by 1,310 · see citing works
Self-citation
Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice
Postic, C., & Girard, J. R. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34275 · Cited by 1,200 · see citing works
Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes
Muoio, D. M., & Newgard, C. B. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2327 · Cited by 1,177 · see citing works
The 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 1,136 · see citing works
Self-citation
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
Self-citation
Insulin Resistance: From Mechanisms to Therapeutic Strategies
Lee, S.-H., Park, S., & Choi, C. S. (2021) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2021.0280 · Cited by 1,179 · see citing works
Self-citation
Triglyceride Metabolism in the Liver
Alves‐Bezerra, M., & Cohen, D. E. (2017) · Comprehensive physiology · doi:10.1002/cphy.c170012 · Cited by 1,229 · see citing works
Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction
Morino, K., Petersen, K. F., & Shulman, G. I. (2006) · Diabetes · doi:10.2337/db06-s002 · Cited by 853 · see citing works
Self-citation
Etiology of Insulin Resistance
Petersen, K. F., & Shulman, G. I. (2006) · The American Journal of Medicine · doi:10.1016/j.amjmed.2006.01.009 · Cited by 825 · see citing works
Self-citation
The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome
Petersen, K. F., Dufour, S., Savage, D. B., Bilz, S., Solomon, G., Yonemitsu, S., Cline, G. W., Befroy, D., Zemany, L., Kahn, B. B., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705408104 · Cited by 759 · see citing works
Self-citation
GRP78 expression inhibits insulin and ER stress–induced SREBP-1c activation and reduces hepatic steatosis in mice
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
Nonalcoholic Fatty Liver Disease, Hepatic Insulin Resistance, and Type 2 Diabetes
Birkenfeld, A. L., & Shulman, G. I. (2013) · Hepatology · doi:10.1002/hep.26672 · Cited by 740 · see citing works
Self-citation
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
Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease
Kumashiro, N., Erion, D. M., Zhang, D., Kahn, M., Beddow, S. A., Chu, X., Still, C. D., Gerhard, G. S., Han, X., Dziura, J., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113359108 · Cited by 585 · see citing works
Self-citation
Sphingolipids, Insulin Resistance, and Metabolic Disease: New Insights from in Vivo Manipulation of Sphingolipid Metabolism
Holland, W. L., & Summers, S. A. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0025 · Cited by 585 · see citing works
Dissociation of Hepatic Steatosis and Insulin Resistance in Mice Overexpressing DGAT in the Liver
Monetti, M., Levin, M. C., Watt, M. J., Sajan, M. P., Marmor, S., Hubbard, B. K., Stevens, R. D., Bain, J. R., Newgard, C. B., Farese, R. V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.005 · Cited by 511 · see citing works
Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease
Samuel, V. T., Liu, Z.-X., Wang, A., Beddow, S. A., Geisler, J. G., Kahn, M., Zhang, X.-M., Monia, B. P., Bhanot, S., & Shulman, G. I. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30400 · Cited by 497 · see citing works
Self-citation
Insulin Resistance, Obesity and Lipotoxicity
Yazıcı, D., & Sezer, H. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_12 · Cited by 507 · see citing works
Diacylglycerol-mediated insulin resistance
Erion, D. M., & Shulman, G. I. (2010) · Nature Medicine · doi:10.1038/nm0410-400 · Cited by 493 · see citing works
Self-citation
Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals
Boden, G., Duan, X., Homko, C., Molina, E. J., Song, W., Perez, O., Cheung, P., & Merali, S. (2008) · Diabetes · doi:10.2337/db08-0604 · Cited by 468 · see citing works
Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis
Takeuchi, K., & Reue, K. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90958.2008 · Cited by 463 · see citing works
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 · see citing works
Acyl-CoA Metabolism and Partitioning
Grevengoed, T. J., Klett, E. L., & Coleman, R. (2014) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071813-105541 · Cited by 444 · see citing works
Self-citation
Mitochondrial 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 432 · see citing works
Diacylglycerol, when simplicity becomes complex
Carrasco, S., & Mérida, I. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.11.004 · Cited by 423 · see citing works
Genetic control of de novo lipogenesis: role in diet-induced obesity
Strable, M. S., & Ntambi, J. M. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409231003667500 · Cited by 415 · see citing works
Role of diacylglycerol activation of PKCθ in lipid-induced muscle insulin resistance in humans
Szendroedi, J., Yoshimura, T., Phielix, E., Koliaki, C., Marcucci, M., Zhang, D., Jelenik, T., Müller, J., Herder, C., Nowotny, P., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409229111 · Cited by 415 · see citing works
Self-citation
Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men
Petersen, K. F., Dufour, S., Feng, J., Befroy, D., Dziura, J., Man, C. D., Cobelli, C., & Shulman, G. I. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608537103 · Cited by 403 · see citing works
Self-citation
Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women
Kars, M., Yang, L., Gregor, M. F., Mohammed, B. S., Pietka, T., Finck, B. N., Patterson, B. W., Horton, J. D., Mittendorfer, B., Hotamışlıgil, G. S., et al. (2010) · Diabetes · doi:10.2337/db10-0308 · Cited by 400 · see citing works
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 · see citing works
Self-citation
Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance
Choi, C. S., Savage, D. B., Kulkarni, A., Yu, X. X., Liu, Z.-X., Morino, K., Kim, S., Distefano, A., Samuel, V. T., Neschen, S., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704213200 · Cited by 383 · see citing works
Self-citation
Estrogen treatment after ovariectomy protects against fatty liver and may improve pathway-selective insulin resistance
Zhu, L., Brown, W. C., Cai, Q., Krust, A., Chambon, P., McGuinness, O. P., & Stafford, J. M. (2013) · Diabetes · doi:10.2337/db11-1718 · Cited by 326 · see citing works
Mammalian Triacylglycerol Metabolism: Synthesis, Lipolysis, and Signaling
Coleman, R., & Mashek, D. G. (2011) · Chemical Reviews · doi:10.1021/cr100404w · Cited by 332 · see citing works
Self-citation
Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity
Choi, C. S., Savage, D. B., Abu-Elheiga, L., Liu, Z.-X., Kim, S., Kulkarni, A., Distefano, A., Hwang, Y.-J., Reznick, R. M., Codella, R., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706794104 · Cited by 325 · see citing works
Self-citation
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 315 · see citing works
Self-citation
Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance
Lee, H.-Y., Choi, C. S., Birkenfeld, A. L., Alves, T. C., Jornayvaz, F. R., Jurczak, M. J., Zhang, D., Woo, D. K., Shadel, G. S., Ladiges, W., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.004 · Cited by 319 · see citing works
Self-citation
Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance
Juárez, R. G. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26991 · Cited by 298 · see citing works
The Role of Ceramides in Insulin Resistance
Sokołowska, E., & Błachnio-Zabielska, A. U. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00577 · Cited by 298 · see citing works
Glycerol-3-phosphate acyltransferases: Rate limiting enzymes of triacylglycerol biosynthesis
Wendel, A. A., Lewin, T. M., & Coleman, R. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2008.10.010 · Cited by 292 · see citing works
Self-citation
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 · see citing works
Akt2 Is Required for Hepatic Lipid Accumulation in Models of Insulin Resistance
Leavens, K. F., Easton, R., Shulman, G. I., Previs, S. F., & Birnbaum, M. J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.10.004 · Cited by 278 · see citing works
Self-citation
Paradoxical effects of increased expression of PGC-1α on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism
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 · see citing works
Self-citation
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
Self-citation
Fructose induced lipogenesis: from sugar to fat to insulin resistance
Samuel, V. T. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.10.003 · Cited by 261 · see citing works
Adipocyte lipolysis: from molecular mechanisms of regulation to disease and therapeutics
Yang, A., & Mottillo, E. P. (2020) · Biochemical Journal · doi:10.1042/bcj20190468 · Cited by 250 · see citing works
Molecular identification of microsomal acyl-CoA:glycerol-3-phosphate acyltransferase, a key enzyme in de novo triacylglycerol synthesis
Cao, J., Li, J., Li, D., Tobin, J. F., & Gimeno, R. E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609140103 · Cited by 245 · see citing works
Triglyceride Metabolism in the Liver
Alves‐Bezerra, M., & Cohen, D. E. (2018) · Comprehensive physiology · doi:10.1002/j.2040-4603.2018.tb00008.x · Cited by 250 · see citing works
Liver-specific Loss of Long Chain Acyl-CoA Synthetase-1 Decreases Triacylglycerol Synthesis and β-Oxidation and Alters Phospholipid Fatty Acid Composition
Li, L. O., Ellis, J. M., Paich, H. A., Wang, S., Gong, N., Altshuller, G., Thresher, R., Koves, T. R., Watkins, S. M., Muoio, D. M., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.022467 · Cited by 236 · see citing works
Self-citation
Multiomics study of nonalcoholic fatty liver disease
Sveinbjörnsson, G., Ulfarsson, M. O., Þórólfsdóttir, R. B., Jónsson, B. A., Einarsson, E., Gunnlaugsson, G., Rögnvaldsson, S., Arnar, D. O., Baldvinsson, M., Bjarnason, R. G., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01199-5 · Cited by 242 · see citing works
Acyl-CoA synthesis, lipid metabolism and lipotoxicity
Li, L. O., Klett, E. L., & Coleman, R. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.024 · Cited by 241 · see citing works
Self-citation
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
Self-citation
n-3 Fatty Acids Preserve Insulin Sensitivity In Vivo in a Peroxisome Proliferator–Activated Receptor-α–Dependent Manner
Neschen, S., Morino, K., Dong, J., Wang-Fischer, Y., Cline, G. W., Romanelli, A. J., Rossbacher, J. C., Moore, I. K., Regittnig, W., Muñoz, D. S., et al. (2007) · Diabetes · doi:10.2337/db06-1206 · Cited by 233 · see citing works
Self-citation
High Sugar-Induced Insulin Resistance in Drosophila Relies on the Lipocalin Neural Lazarillo
Pasco, M. Y., & Léopold, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036583 · Cited by 225 · see citing works
Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice
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 229 · see citing works
Intrahepatic Diacylglycerol Content Is Associated With Hepatic Insulin Resistance in Obese Subjects
Magkos, F., Su, X., Bradley, D. P., Fabbrini, E., Conte, C., Eagon, J. C., Varela, J. E., Brunt, E. M., Patterson, B. W., & Klein, S. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.03.003 · Cited by 223 · see citing works
Deletion of the Mammalian INDY Homolog Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in Mice
Birkenfeld, A. L., Lee, H., Guebre‐Egziabher, F., Alves, T. C., Jurczak, M. J., Jornayvaz, F. R., Zhang, D., Hsiao, J. J., Martín‐Montalvo, A., Fischer‐Rosinsky, A., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.06.009 · Cited by 212 · see citing works
Self-citation
A Common Variant in the Patatin-Like Phospholipase 3 Gene ( PNPLA3 ) Is Associated with Fatty Liver Disease in Obese Children and Adolescents
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 214 · see citing works
Self-citation
Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease
Chen, Y., Du, X., Kuppa, A., Feitosa, M. F., Bielak, L. F., O’Connell, J. R., Musani, S. K., Guo, X., Kahali, B., Chen, V. L., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01497-6 · Cited by 215 · see citing works
A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain
Jornayvaz, F. R., Jurczak, M. J., Lee, H., Birkenfeld, A. L., Frederick, D. W., Zhang, D., Zhang, X., Samuel, V. T., & Shulman, G. I. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00361.2010 · Cited by 212 · see citing works
Self-citation
Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonist #
Cable, E. E., Finn, P. D., Stebbins, J. W., Hou, J., Ito, B. R., van Poelje, P. D., Linemeyer, D. L., & Erion, M. D. (2008) · Hepatology · doi:10.1002/hep.22572 · Cited by 206 · see citing works
The Role of Peroxisome Proliferator-Activated Receptor γ Coactivator-1 β in the Pathogenesis of Fructose-Induced Insulin Resistance
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 · see citing works
Self-citation
Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance
Hernández, E. Á., KAHL, S., Seelig, A., Begovatz, P., Irmler, M., Kupriyanova, Y., Nowotny, B., Nowotny, P., Herder, C., Barosa, C., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89444 · Cited by 195 · see citing works
Self-citation
Mouse Cardiac Acyl Coenzyme A Synthetase 1 Deficiency Impairs Fatty Acid Oxidation and Induces Cardiac Hypertrophy
Ellis, J. M., Mentock, S. M., DePetrillo, M. A., Koves, T. R., Sen, S., Watkins, S. M., Muoio, D. M., Cline, G. W., Taegtmeyer, H., Shulman, G. I., et al. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.01085-10 · Cited by 194 · see citing works
Self-citation
Physical activity and liver diseases
Berzigotti, A., Saran, U., & Dufour, J. (2015) · Hepatology · doi:10.1002/hep.28132 · Cited by 186 · see citing works
Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance
Choi, C. S., Fillmore, J. J., Kim, J. K., Liu, Z., Kim, S., Collier, E. F., Kulkarni, A. S., Distefano, A. G., Hwang, Y.-J., Kahn, M., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci13579 · Cited by 182 · see citing works
Self-citation
Hypomorphic mutation of PGC-1β causes mitochondrial dysfunction and liver insulin resistance.
Vianna, C. R., Huntgeburth, M., Coppari, R., Choi, C. S., Lin, J., Krauss, S., Barbatelli, G., Tzameli, I., Kim, Y.-B., Cinti, S., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.11.003 · Cited by 181 · see citing works
Self-citation
Comparison of Lipid and Fatty Acid Composition of the Liver, Subcutaneous and Intra‐abdominal Adipose Tissue, and Serum
Kotronen, A., Seppänen‐Laakso, T., Westerbacka, J., Kiviluoto, T. A., Arola, J. T., Ruskeepää, A., Yki‐Järvinen, H., & Orešič, M. (2009) · Obesity · doi:10.1038/oby.2009.326 · Cited by 179 · see citing works
Lipid oversupply, selective insulin resistance, and lipotoxicity: Molecular mechanisms
Chavez, J. A., & Summers, S. A. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.015 · Cited by 167 · see citing works
Insulin signaling to hepatic lipid metabolism in health and disease
Leavens, K. F., & Birnbaum, M. J. (2011) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2011.562481 · Cited by 162 · see citing works
CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance
Brown, J. M., Betters, J. L., Lord, C. C., Ma, Y., Han, X., Yang, K., Alger, H. M., Melchior, J., Sawyer, J. K., Shah, R., et al. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m010256 · Cited by 154 · see citing works
Self-citation
AGPAT6 Is a Novel Microsomal Glycerol-3-phosphate Acyltransferase
Chen, Y., Kuo, M., Li, S., Bui, H. H., Peake, D. A., Sanders, P. E., Thibodeaux, S. J., Chu, S., Qian, Y., Zhao, Y., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708151200 · Cited by 151 · see citing works
Regulation of fat metabolism in the liver: link to non-alcoholic hepatic steatosis and impact of physical exercise
Lavoie, J.-M., & Gauthier, M. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6600-y · Cited by 149 · see citing works
Sensitivity of Lipid Metabolism and Insulin Signaling to Genetic Alterations in Hepatic Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α Expression
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 148 · see citing works
Self-citation
Exome-wide association study on alanine aminotransferase identifies sequence variants in the GPAM and APOE associated with fatty liver disease
Jamialahmadi, O., Mancina, R. M., Ciociola, E., Tavaglione, F., Luukkonen, P. K., Baselli, G., Malvestiti, F., Thuillier, D., Raverdy, V., Männistö, V., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.12.023 · Cited by 148 · see citing works
Lipid Mediators of Insulin Resistance
Holland, W. L., Knotts, T. A., Chavez, J. A., Wang, L.-P., Hoehn, K. L., & Summers, S. A. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2007.tb00327.x · Cited by 147 · see citing works
Lipid metabolism in skeletal muscle: generation of adaptive and maladaptive intracellular signals for cellular function
Watt, M. J., & Hoy, A. J. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00561.2011 · Cited by 142 · see citing works
Activation of PPARα Ameliorates Hepatic Insulin Resistance and Steatosis in High Fructose–Fed Mice Despite Increased Endoplasmic Reticulum Stress
Chan, S. M. H., Sun, R., Zeng, X., Choong, Z.-H., Wang, H., Watt, M. J., & Ye, J. (2013) · Diabetes · doi:10.2337/db12-1397 · Cited by 145 · see citing works
Chronic Inflammation—A Link between Nonalcoholic Fatty Liver Disease (NAFLD) and Dysfunctional Adipose Tissue
Petrescu, M. D., Vlaicu, S. I., Ciumărnean, L., Milaciu, M. V., Mărginean, C., Florea, M., Vesa, Ș. C., & Popa, M. (2022) · Medicina · doi:10.3390/medicina58050641 · Cited by 150 · see citing works
Dissociation of Inositol-requiring Enzyme (IRE1α)-mediated c-Jun N-terminal Kinase Activation from Hepatic Insulin Resistance in Conditional X-box-binding Protein-1 (XBP1) Knock-out Mice
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 142 · see citing works
Self-citation
E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis
Denechaud, P., López‐Mejía, I. C., Giralt, A., Lai, Q., Blanchet, É., Delacuisine, B., Nicolay, B., Dyson, N. J., Bonner, C., Pattou, F. N., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81542 · Cited by 142 · see citing works
Thematic Review Series: Glycerolipids. Mammalian glycerol-3-phosphate acyltransferases: new genes for an old activity
Gimeno, R. E., & Cao, J. (2008) · Journal of Lipid Research · doi:10.1194/jlr.r800013-jlr200 · Cited by 137 · see citing works
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Mitochondrial Glycerol-3-phosphate Acyltransferase-1 Is Essential inLiver for the Metabolism of ExcessAcyl-CoAs
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ORIGINAL ARTICLE Glycerol-3-Phosphate Acyltransferase 1 Deficiency in ob/ob Mice Diminishes Hepatic Steatosis but Does Not Protect Against Insulin Resistance or Obesity
Wendel, A. A., Li, L. O., Li, Y., Cline, G. W., Shulman, G. I., & Coleman, R. A. (2013)
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Regulation of Triglyceride Metabolism II. Function of mitochondrial GPAT1 in the regulation of triacylglycerol biosynthesis and insulin action
González-Baró, M. R., Lewin, T. M., & Coleman, R. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00553.2006 · Cited by 121 · see citing works
Self-citation

Authors: Neschen, S., Morino, K., Hammond, L. E., Zhang, D., Liu, Z.-X., Romanelli, A. J., Cline, G. W., Pongratz, R. L., Zhang, X.-M., Choi, C. S., Coleman, R. A., & Shulman, G. I.
Affiliations: Howard Hughes Medical Institute (US)
University of North Carolina at Chapel Hill (US)
Yale University (US)
Corresponding author: Shulman, Gerald I.
ORCID: Morino, Katsutaro
Zhang, Dongyan
Cline, Gary W.
Choi, Cheol S.
Coleman, Rosalind A.
Shulman, Gerald I.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2005-07
Volume: 2
Issue: 1
Pages: 55-65
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2005.06.006
OpenAlex: W2006375647
Semantic Scholar: e7251c54287df4fd1cb668ac0f825e2c909f61c2
Cited by: 261
References: 64
Citations by year: 2026: 2 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 12 · 2018: 11 · 2017: 6 · 2016: 4 · 2015: 12 · 2014: 16 · 2013: 13 · 2012: 20
FWCI: 13.15
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2938 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (F31GM020920, F31 GM20920)
National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK40936, R01DK56598, U24DK59635, R01DK040936, U24DK059635, R01DK056598)
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 › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords: hepatic steatosis, hepatic insulin resistance, knockout mice, high-fat diet, diacylglycerol, protein kinase C, triglycerides, insulin sensitivity, lipid metabolism
MeSH terms: Acetyl-CoA Carboxylase, Acetyl Coenzyme A, Animals, Dietary Fats, Diglycerides, Fasting, Fatty Liver, Glucose Tolerance Test, Glycerol-3-Phosphate O-Acyltransferase, Insulin Resistance, Liver, Lysophospholipids, Male, Malonyl Coenzyme A, Mice, Inbred C57BL, Mitochondria, Multienzyme Complexes, Phenotype, Triglycerides, Protein Serine-Threonine Kinases, Mice, Knockout, Mice, AMP-Activated Protein Kinases

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Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice

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