Cited by 879Adipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and ObesityLipid metabolism and biosynthesis

The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.

Lipotoxic Diseases

Unger, Roger H.·2002·Annual Review of Medicine

DOI 10.1146/annurev.med.53.082901.104057

Open this paper in CoChat — free account

Abstract

I review evidence that leptin is a liporegulatory hormone that controls lipid homeostasis in nonadipose tissues during periods of overnutrition. When adipocytes store excess calories as triacylglycerol (TG), leptin secretion rises so as to prevent accumulation of lipids in nonadipose tissues, which are not adapted for TG storage. Whenever leptin action is lacking, whether through leptin deficiency or leptin resistance, overnutrition causes disease of nonadipose tissues with generalized steatosis, lipotoxicity, and lipoapoptosis. Examples of such disorders of liporegulation include generalized lipodystrophies, mutations of leptin and leptin receptor genes, and diet-induced obesity. Lipotoxicity of pancreatic beta-cells, myocardium, and skeletal muscle leads, respectively, to type 2 diabetes, cardiomyopathy, and insulin resistance. In humans this constellation of abnormalities is referred to as the metabolic syndrome, a major health problem in the United States. When lipids overaccumulate in nonadipose tissues during overnutrition, fatty acids enter deleterious pathways such as ceramide production, which, through increased nitric oxide formation, causes apoptosis of lipid-laden cells, such as beta-cells and cardiomyocytes. Lipoapoptosis can be prevented by caloric restriction, by thiazolidinedione treatment, and by administration of nitric oxide blockers. There is now substantial evidence that complications of human obesity may reflect lipotoxicity similar to that described in rodents.

Integrity signals

Registry

Crossref · 10.1146/annurev.med.53.082901.104057

Cites

73 of 73 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
Effects of the obese Gene Product on Body Weight Regulation in ob / ob Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017
Recombinant Mouse OB Protein: Evidence for a Peripheral Signal Linking Adiposity and Central Neural Networks
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243
Congenital leptin deficiency is associated with severe early-onset obesity in humans
Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., et al. (1997) · Nature · doi:10.1038/43185 · Cited by 2,936
Obesity and the regulation of energy balance
Spiegelman, B. M., & Flier, J. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00240-9 · Cited by 2,398
A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.-M., et al. (1998) · Nature · doi:10.1038/32911 · Cited by 2,346
Abnormal splicing of the leptin receptor in diabetic mice
Lee, G.-H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., & Friedman, J. M. (1996) · Nature · doi:10.1038/379632a0 · Cited by 2,327
Programmed Cell Death Induced by Ceramide
Obeid, L. M., Linardic, C. M., Karolak, L. A., & Hannun, Y. A. (1993) · Science · doi:10.1126/science.8456305 · Cited by 1,794
Adipose Tissue as an Endocrine Organ
Ahima, R. S., & Flier, J. S. (2000) · Trends in Endocrinology & Metabolism · doi:10.1016/s1043-2760(00)00301-5 · Cited by 1,608

Show all 71 references

Research works printed but not linked: 4

Wang Z-W, 1999, Proc. Natl. Acad. Sci. USA, 96, 100373
Koyama K, 1997, Am. J. Physiol., 273, E708
10.1210/jc.83.3.931 · DOI
10.1042/0264-6021:3450161 · DOI

Sorted by citations

Items 101–200 of 879

Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant and Diabetic Individuals
Moon, H., Dalamaga, Μ., Kim, S. Y., Pοlyzos, S. A., Hamnvik, O. R., Magkos, F., Paruthi, J., & Mantzoros, C. S. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1053 · Cited by 265
Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats
Ouwens, D. M., Boer, C., Fodor, M., de Galan, P., Heine, R. J., Maassen, J. A., & Diamant, M. (2005) · Diabetologia · doi:10.1007/s00125-005-1755-x · Cited by 256
PATHOPHYSIOLOGY OF TYPE 2 DIABETES
Scheen, A. J. (2003) · Acta Clinica Belgica · doi:10.1179/acb.2003.58.6.001 · Cited by 250
Monounsaturated Fatty Acids in Obesity-Related Inflammation
Ravaut, G., Légiot, A., Bergeron, K., & Mounier, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010330 · Cited by 272
Fate of fat: The role of adipose triglyceride lipase in lipolysis
Zimmermann, R., Lass, A., Haemmerle, G., & Zechner, R. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2008.10.005 · Cited by 250
Leptin‐induced signal transduction pathways
Hegyi, K., Fülöp, K., Kovács, K., Tóth, S., & Falus, A. (2004) · Cell Biology International · doi:10.1016/j.cellbi.2003.12.003 · Cited by 250
Suicidal death of erythrocytes in recurrent hemolytic uremic syndrome
Lang, P. A., Beringer, O., Nicolay, J. P., Amon, O., Kempe, D. S., Hermle, T. F., Attanasio, P., Akel, A., Schäfer, R., Friedrich, B., et al. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-006-0058-0 · Cited by 239
Central Ceramide-Induced Hypothalamic Lipotoxicity and ER Stress Regulate Energy Balance
Contreras, C., González‐García, I., Martínez‐Sánchez, N., Seoane‐Collazo, P., Jacas, J., Morgan, D. A., Serra, D., Gallego, R., González, F., Casals, N., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.057 · Cited by 244
Metabolic Syndrome and Vascular Disease
DEEDWANIA, P. C. (2004) · Circulation · doi:10.1161/01.cir.0000110642.73995.bf · Cited by 234
Adipocyte Protein S3-12 Coats Nascent Lipid Droplets
Wolins, N. E., Skinner, J. R., Schoenfish, M. J., Tzekov, A., Bensch, K. G., & Bickel, P. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304025200 · Cited by 235
Leptin Induces Hypertrophy via Endothelin-1–Reactive Oxygen Species Pathway in Cultured Neonatal Rat Cardiomyocytes
Xu, F.-P., Chen, M.-S., Wang, Y.-Z., Yi, Q., Lin, S.-B., Chen, A. F., & Luo, J.-D. (2004) · Circulation · doi:10.1161/01.cir.0000140766.52771.6d · Cited by 234
Fatty acid metabolism is enhanced in type 2 diabetic hearts
Carley, A. N., & Severson, D. L. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.03.005 · Cited by 232
Regulation of lipid metabolism by soy protein and its implication in diseases mediated by lipid disorders
Torres, N., Torre-Villalvazo, I., & Tovar, A. R. (2005) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2005.11.005 · Cited by 235
Metabolic syndrome and non-alcoholic fatty liver disease
Almeda‐Valdés, P., Ramos, D. C., & Aguilar-Salinas, C. A. (2009) · Annals of Hepatology · doi:10.1016/s1665-2681(19)31822-8 · Cited by 234
Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy†
Javor, E. D., Ghany, M. G., Cochran, E. K., Oral, E. A., DePaoli, A. M., Premkumar, A., Kleiner, D. E., & Gorden, P. (2005) · Hepatology · doi:10.1002/hep.20672 · Cited by 228
Ubiquitinated-Protein Aggregates Form in Pancreatic β-Cells During Diabetes-Induced Oxidative Stress and Are Regulated by Autophagy
Kaniuk, N. A., Kiràly, M. A., Bates, H. E., Vranić, M., Volchuk, A., & Brumell, J. H. (2007) · Diabetes · doi:10.2337/db06-1160 · Cited by 226
Cardiorespiratory Fitness and Short-term Complications After Bariatric Surgery
McCullough, P. A., Gallagher, M. J., deJong, A., Sandberg, K. R., Trivax, J. E., Alexander, D., Kasturi, G. C., Jafri, S. M. A., Krause, K. R., Chengelis, D. L., et al. (2006) · CHEST Journal · doi:10.1378/chest.130.2.517 · Cited by 222
Transcriptional regulatory networks in lipid metabolism control ABCA1 expression
Schmitz, G., & Langmann, T. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.04.004 · Cited by 222
Toward fingerprinting cellular lipidomes directly from biological samples by two-dimensional electrospray ionization mass spectrometry
Han, X., Yang, J., Cheng, H., Ye, H., & Gross, R. W. (2004) · Analytical Biochemistry · doi:10.1016/j.ab.2004.04.004 · Cited by 219
Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo
Saha, A. K., Avilucea, P. R., Ye, J.-M., Assifi, M. M., Kraegen, E. W., & Ruderman, N. B. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.12.120 · Cited by 220
Adipose tissue plasticity from WAT to BAT and in between
Lee, Y., Mottillo, E. P., & Granneman, J. G. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.011 · Cited by 236
AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise
Ruderman, N. B., Park, H., Kaushik, V. K., Dean, D., Constant, S., Prentki, M., & Saha, A. K. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01164.x · Cited by 217
Adipogenesis and fat-cell function in obesity and diabetes
Camp, H. S., Ren, D., & Leff, T. (2002) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(02)02396-1 · Cited by 212
Enlarged Waist Combined With Elevated Triglycerides Is a Strong Predictor of Accelerated Atherogenesis and Related Cardiovascular Mortality in Postmenopausal Women
Tankó, L. B., Bagger, Y. Z., Qin, G., Alexandersen, P., Larsen, P. J., & Christiansen, C. (2005) · Circulation · doi:10.1161/01.cir.0000161801.65408.8d · Cited by 210
The lipin protein family: Dual roles in lipid biosynthesis and gene expression
Reue, K., & Zhang, P. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.11.014 · Cited by 209
Free Fatty Acid-induced β-Cell Defects Are Dependent on Uncoupling Protein 2 Expression
Joseph, J. W., Koshkin, V., Saleh, M. C., Sivitz, W. I., Zhang, C.-Y., Lowell, B. B., Chan, C. B., & Wheeler, M. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409189200 · Cited by 206
The Physiology of Cellular Liporegulation
Unger, R. H. (2003) · Annual Review of Physiology · doi:10.1146/annurev.physiol.65.092101.142622 · Cited by 208
Self-citation
Metabolic risks identified by the combination of enlarged waist and elevated triacylglycerol concentration
Kahn, H. S., & Valdez, R. A. (2003) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/78.5.928 · Cited by 203
Identification and Characterization of Murine SCD4, a Novel Heart-specific Stearoyl-CoA Desaturase Isoform Regulated by Leptin and Dietary Factors
Miyazaki, M., Jacobson, M. J., Man, W. C., Cohen, P., Asilmaz, E., Friedman, J. M., & Ntambi, J. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304724200 · Cited by 204
Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet
Pu, P., Gao, D.-M., Salim, M., Chen, J., Zhang, J., Zhou, X., Nai-jing, Z., Xie, J., & Jiang, H. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2011.11.026 · Cited by 203
Myocardial Steatosis and Biventricular Strain and Strain Rate Imaging in Patients With Type 2 Diabetes Mellitus
Ng, A. C. T., Delgado, V., Bertini, M., van der Meer, R. W., Rijzewijk, L. J., Ewe, S. H., Siebelink, H.-M., Smit, J. W. A., Diamant, M., Romijn, J. A., et al. (2010) · Circulation · doi:10.1161/circulationaha.110.955542 · Cited by 202
Anti-obesity therapy: from rainbow pills to polyagonists
Müller, T. D., Clemmensen, C., Finan, B., DiMarchi, R. D., & Tschöp, M. H. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014803 · Cited by 199
The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-α in 3T3-L1 adipocytes and is a target for transactivation by PPARγ
Kim, J. Y., Tillison, K., Lee, J., Rearick, D. A., & Smas, C. M. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00317.2005 · Cited by 207
Adipose Overexpression of Desnutrin Promotes Fatty Acid Use and Attenuates Diet-Induced Obesity
Ahmadian, M., Duncan, R. E., Varady, K. A., Frasson, D., Hellerstein, M. K., Birkenfeld, A. L., Samuel, V. T., Shulman, G. I., Wang, Y., Kang, C., et al. (2009) · Diabetes · doi:10.2337/db08-1644 · Cited by 199
Lipotoxic endoplasmic reticulum stress, β cell failure, and type 2 diabetes mellitus
Biden, T. J., Boslem, E., Chu, K. Y., & Sue, N. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.02.003 · Cited by 200
Role of Peroxisome Proliferator-Activated Receptor-γ in the Glucose-Sensing Apparatus of Liver and β-Cells
Kim, H., & Ahn, Y. (2004) · Diabetes · doi:10.2337/diabetes.53.2007.s60 · Cited by 194
Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice
Cao, K. J., Xu, J., Zou, X., Li, Y., Chen, C., Zheng, A., Li, H., Li, H., Szeto, I. M., Shi, Y., et al. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.11.029 · Cited by 199
Lipidomics at the Interface of Structure and Function in Systems Biology
Gross, R. W., & Han, X. (2011) · Chemistry & Biology · doi:10.1016/j.chembiol.2011.01.014 · Cited by 196
Transcriptional Regulation of Bim by FoxO3A Mediates Hepatocyte Lipoapoptosis
Barreyro, F. J., Kobayashi, S., Bronk, S. F., Werneburg, N. W., Malhi, H., & Gores, G. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704391200 · Cited by 190
Interleukin-6 Regulation of AMP-Activated Protein Kinase
Ruderman, N. B., Keller, C., Richard, A.-M. T., Saha, A. K., Luo, Z., Xiang, X., Giralt, M., Ritov, V. B., Menshikova, E. V., Kelley, D. E., et al. (2006) · Diabetes · doi:10.2337/db06-s007 · Cited by 191
Lipidomics: a new window to biomedical frontiers
Orešič, M., Hänninen, V. A., & Vidal‐Puig, A. (2008) · Trends in biotechnology · doi:10.1016/j.tibtech.2008.09.001 · Cited by 189
The multi-dimensional regulation of gene expression by fatty acids: polyunsaturated fats as nutrient sensors
Clarke, S. D. (2004) · Current Opinion in Lipidology · doi:10.1097/00041433-200402000-00004 · Cited by 188
Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine
Unger, R. H. (2005) · Biochimie · doi:10.1016/j.biochi.2004.11.014 · Cited by 184
Self-citation
Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates protein-tyrosine phosphatase 1B in muscle
Rahman, S. M., Dobrzyń, A., Dobrzyń, P., Lee, S., Miyazaki, M., & Ntambi, J. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1934571100 · Cited by 183
Fast flip-flop of cholesterol and fatty acids in membranes: implications for membrane transport proteins
Hamilton, J. A. (2003) · Current Opinion in Lipidology · doi:10.1097/00041433-200306000-00006 · Cited by 184
Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation
Lelliott, C. J., & Vidal‐Puig, A. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802854 · Cited by 187
The Evolving Role of Leptin and Adiponectin in Chronic Liver Diseases
Tsochatzis, E. A., Papatheodoridis, G., & Archimandritis, A. J. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00848.x · Cited by 190
Shotgun Lipidomics Identifies Cardiolipin Depletion in Diabetic Myocardium Linking Altered Substrate Utilization with Mitochondrial Dysfunction
Han, X., Yang, J., Cheng, H., Yang, K., Abendschein, D. R., & Gross, R. W. (2005) · Biochemistry · doi:10.1021/bi051908a · Cited by 181
Management of non-alcoholic fatty liver disease
Petroni, M. L., Brodosi, L., Bugianesi, E., & Marchesini, G. (2021) · BMJ · doi:10.1136/bmj.m4747 · Cited by 193
Cardiac Myocyte Apoptosis Is Associated With Increased DNA Damage and Decreased Survival in Murine Models of Obesity
Barouch, L. A., Gao, D., Chen, L., Miller, K. L., Xu, W., Phan, A. C., Kittleson, M. M., Minhas, K. M., Berkowitz, D. E., Wei, C., et al. (2006) · Circulation Research · doi:10.1161/01.res.0000199348.10580.1d · Cited by 180
The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment
Ranganathan, G., Ünal, R., Pokrovskaya, I. D., Yao‐Borengasser, A., Phanavanh, B., Lecka‐Czernik, B., Rasouli, N., & Kern, P. A. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600248-jlr200 · Cited by 182
Cytosolic Lipid Droplets Increase in Size by Microtubule-Dependent Complex Formation
Boström, P., Rutberg, M., Ericsson, J., Holmdahl, P., Andersson, L. K., Frohman, M. A., Borén, J., & Olofsson, S. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000179676.41064.d4 · Cited by 183
Obesity, Peroxisome Proliferator-Activated Receptor, and Atherosclerosis in Type 2 Diabetes
Blaschke, F., Takata, Y., Caglayan, E., Law, R. E., & Hsueh, W. A. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000191663.12164.77 · Cited by 176
The pancreatic β cell is a key site for mediating the effects of leptin on glucose homeostasis
Covey, S. D., Wideman, R. D., McDonald, C. M., Unniappan, S., Huynh, F. K., Asadi, A., Speck, M., Webber, T. D., Chua, S. C., & Kieffer, T. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.09.005 · Cited by 179
The Role of Zinc and Copper in Insulin Resistance and Diabetes Mellitus
Bjørklund, G., Dadar, M., Pivina, L. M., Doşa, M. D., Semenova, Y. M., & Aaseth, J. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190902122155 · Cited by 178
Bax inhibition protects against free fatty acid-induced lysosomal permeabilization
Feldstein, A. E., Werneburg, N. W., Li, Z., Bronk, S. F., & Gores, G. J. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00509.2005 · Cited by 174
NF-κB and STAT1 control CXCL1 and CXCL2 gene transcription
Burke, S. J., Lu, D., Sparer, T. E., Masi, T. J., Goff, M. R., Karlstad, M. D., & Collier, J. J. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00347.2013 · Cited by 180
Stearoyl‐CoA desaturase as a new drug target for obesity treatment
Dobrzyń, A., & Ntambi, J. M. (2005) · Obesity Reviews · doi:10.1111/j.1467-789x.2005.00177.x · Cited by 173
Leptin Activates Cardiac Fatty Acid Oxidation Independent of Changes in the AMP-activated Protein Kinase-Acetyl-CoA Carboxylase-Malonyl-CoA Axis
Atkinson, L. L., Fischer, M. A., & Lopaschuk, G. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203813200 · Cited by 174
Visceral obesity and the heart
Mathieu, P., Pîbarot, P., Larose, É., Poirier, P., Marette, A., & Després, J. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.12.001 · Cited by 173
Lipolysis and the integrated physiology of lipid energy metabolism
Wang, S., Soni, K. G., Semache, M., Casavant, S., Fortier, M., Pan, L., & Mitchell, G. A. (2008) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2008.06.012 · Cited by 174
Recent advances in the pathophysiology of nephrolithiasis
Sakhaee, K. (2008) · Kidney International · doi:10.1038/ki.2008.626 · Cited by 169
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 170
Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro
Elbaz, A., Wu, X., Rivas, D., Gimble, J. M., & Duque, G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00751.x · Cited by 169
The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction
Perman, J., Boström, P., Lindbom, M., Lidberg, U., Ståhlman, M., Hägg, D. A., Lindskog, H., Täng, M. S., Ömerovic, E., Hultén, L. M., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43068 · Cited by 168
The role of stearoyl-CoA desaturase in the control of metabolism
Dobrzyń, A., & Ntambi, J. M. (2005) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2005.04.011 · Cited by 169
Interactions of Metabolic Hormones, Adipose Tissue and Exercise
McMurray, R. G., & Hackney, A. C. (2005) · Sports Medicine · doi:10.2165/00007256-200535050-00003 · Cited by 172
AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease
Wong, A., Howie, J., Petrie, J. R., & Lang, C. C. (2009) · Clinical Science · doi:10.1042/cs20080066 · Cited by 170
Ectopic fat accumulation and metabolic syndrome
Rasouli, N., Molavi, B., Elbein, S. C., & Kern, P. A. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00590.x · Cited by 169
Leptin and the Control of Metabolism: Role for Stearoyl-CoA Desaturase-1 (SCD-1)
Cohen, P., & Friedman, J. M. (2004) · Journal of Nutrition · doi:10.1093/jn/134.9.2455s · Cited by 165
Intracellular Lipid Accumulation in Liver and Muscle and the Insulin Resistance Syndrome
Lara‐Castro, C., & Garvey, W. T. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.09.002 · Cited by 167
Metabolomics, a novel tool for studies of nutrition, metabolism and lipid dysfunction
Orešič, M. (2009) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2009.04.018 · Cited by 165
Liver-specific expression of transcriptionally active SREBP-1c is associated with fatty liver and increased visceral fat mass
Knebel, B., Haas, J., Hartwig, S., Jacob, S., Köllmer, C., Nitzgen, U., Muller–Wieland, D., & Kotzka, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031812 · Cited by 162
“This lipid overload has destructive effects on cell functionality and viability, as initially pronounced by Unger in the ‘‘lipoptoxicity hypothesis’’ [1].”
Background
Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing β-oxidation in skeletal muscle
Dobrzyń, A., Dobrzyń, P., Lee, S., Miyazaki, M., Cohen, P., Asilmaz, E., Hardie, D. G., Friedman, J. M., & Ntambi, J. M. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00439.2004 · Cited by 164
Oxidative stress in cardiovascular disease: molecular basis of its deleterious effects, its detection, and therapeutic considerations
Molavi, B., & Mehta, J. L. (2004) · Current Opinion in Cardiology · doi:10.1097/01.hco.0000133657.77024.bd · Cited by 160
Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity
Gregorio, G. B. D., Hensley, L. L., Lü, T., Ranganathan, G., & Kern, P. A. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00189.2003 · Cited by 165
PPARγ-induced cardiolipotoxicity in mice is ameliorated by PPARα deficiency despite increases in fatty acid oxidation
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
Clinical availability of nonalcoholic fatty liver disease as an early predictor of type 2 diabetes mellitus in korean men: 5-year prospective cohort study
Park, S. K., Seo, M. H., Shin, H. C., & Ryoo, J. (2012) · Hepatology · doi:10.1002/hep.26183 · Cited by 159
Antidiabetic effect of total saponins from Entada phaseoloides (L.) Merr. in type 2 diabetic rats
Zheng, T., Shu, G., Yang, Z., Mo, S., Zhao, Y., & Mei, Z. (2011) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2011.12.025 · Cited by 159
db / db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet
Burke, S. J., Batdorf, H. M., Burk, D. H., Noland, R. C., Eder, A. E., Boulos, M. S., Karlstad, M. D., & Collier, J. J. (2017) · Journal of Diabetes Research · doi:10.1155/2017/8503754 · Cited by 164
Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats
Levy, J. R., Clore, J. N., & Stevens, W. D. (2004) · Hepatology · doi:10.1002/hep.20093 · Cited by 156
Effects of Weight Loss and Physical Activity on Muscle Lipid Content and Droplet Size
He, J., Goodpaster, B. H., & Kelley, D. E. (2004) · Obesity Research · doi:10.1038/oby.2004.92 · Cited by 152
Protein restriction during gestation and/or lactation causes adverse transgenerational effects on biometry and glucose metabolism in F1 and F2 progenies of rats
Pinheiro, A. R., Salvucci, I. D. M., Aguila, M. B., & Mandarim-de-Lacerda, C. A. (2008) · Clinical Science · doi:10.1042/cs20070302 · Cited by 153
Brain Adipocytokine Action and Metabolic Regulation
Ahima, R. S., Qi, Y., Singhal, N. S., Jackson, M. B., & Scherer, P. E. (2006) · Diabetes · doi:10.2337/db06-s018 · Cited by 150
Topological Orientation of Acyl-CoA:Diacylglycerol Acyltransferase-1 (DGAT1) and Identification of a Putative Active Site Histidine and the Role of the N Terminus in Dimer/Tetramer Formation
McFie, P. J., Stone, S. L., Banman, S. L., & Stone, S. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.163691 · Cited by 150
Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition
Yu, X., McCorkle, S. K., Wang, M., Lee, Y., Li, J., Saha, A. K., Unger, R. H., & Ruderman, N. B. (2004) · Diabetologia · doi:10.1007/s00125-004-1570-9 · Cited by 151
Self-citation
Adipose Triglyceride Lipase Regulation: An Overview
Cerk, I. K., Wechselberger, L., & Oberer, M. (2017) · Current Protein and Peptide Science · doi:10.2174/1389203718666170918160110 · Cited by 149
Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue
Rasouli, N., Raue, U., Miles, L. M., Lu, T., Gregorio, G. B. D., Elbein, S. C., & Kern, P. A. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00522.2004 · Cited by 149
Tissue-Autonomous Function of Drosophila Seipin in Preventing Ectopic Lipid Droplet Formation
Tian, Y., Bi, J., Shui, G., Liu, Z., Xiang, Y., Liu, Y. M., Wenk, M. R., Yang, H., & Huang, X. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001364 · Cited by 151
Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with Type 2 diabetes mellitus
Pena, M. J., Heerspink, H. J. L., Hellemons, M. E., Friedrich, T., Dallmann, G., Lajer, M., Bakker, S. J. L., Gansevoort, R. T., Rossing, P. R., de Zeeuw, D., et al. (2014) · Diabetic Medicine · doi:10.1111/dme.12447 · Cited by 151
Adiponectin-Resistance in Obesity
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_18 · Cited by 149
Causes and Characteristics of Diabetic Cardiomyopathy
Wang, J., Song, Y., Wang, Q., Kralik, P. M., & Epstein, P. N. (2006) · The Review of Diabetic Studies · doi:10.1900/rds.2006.3.108 · Cited by 145
New insights into insulin resistance in the diabetic heart
Gray, S., & Kim, J. K. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.05.001 · Cited by 147
Adipokines in Nonalcoholic Steatohepatitis: From Pathogenesis to Implications in Diagnosis and Therapy
Tsochatzis, E. A., Papatheodoridis, G., & Archimandritis, A. J. (2009) · Mediators of Inflammation · doi:10.1155/2009/831670 · Cited by 147
Protein Kinase C δ Activation and Translocation to the Nucleus Are Required for Fatty Acid-Induced Apoptosis of Insulin-Secreting Cells
Eitel, K., Staiger, H., Rieger, J., Mischak, H., Brandhorst, H., Brendel, M. D., Bretzel, R. G., Häring, H., & Kellerer, M. (2003) · Diabetes · doi:10.2337/diabetes.52.4.991 · Cited by 142
Role of diet and fuel overabundance in the development and progression of heart failure
Chess, D. J., & Stanley, W. C. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn074 · Cited by 143
Gene Expression Profiles of Nondiabetic and Diabetic Obese Mice Suggest a Role of Hepatic Lipogenic Capacity in Diabetes Susceptibility
Hong, L., Rabaglia, M. E., Stoehr, J. P., Nadler, S. T., Schueler, K. L., Zou, F., Yandell, B. S., & Attie, A. (2003) · Diabetes · doi:10.2337/diabetes.52.3.688 · Cited by 141
In beta-cells, mitochondria integrate and generate metabolic signals controlling insulin secretion
Maechler, P., Carobbio, S., & Rubi, B. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.12.006 · Cited by 140
Raman Imaging of Small Biomolecules
Shen, Y., Hu, F., & Min, W. (2019) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-052118-115500 · Cited by 138
Angiopoietin-like proteins: potential new targets for metabolic syndrome therapy
Oike, Y., Akao, M., Kubota, Y., & Suda, T. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2005.08.002 · Cited by 140

Authors: Unger, R. H.
Affiliations: Dallas VA Medical Center (US)
Corresponding author: Unger, Roger H.
Venue: Annual Review of Medicine
Publisher: Annual Reviews
Published: 2002-02
Volume: 53
Issue: 1
Pages: 319-336
ISSN: 0066-4219 (ISSN-L)
1545-326X
DOI: 10.1146/annurev.med.53.082901.104057
OpenAlex: W4254261652
Cited by: 875
References: 71
Citations by year: 2026: 9 · 2025: 14 · 2024: 25 · 2023: 15 · 2022: 18 · 2021: 31 · 2020: 22 · 2019: 21 · 2018: 22 · 2017: 30 · 2016: 32 · 2015: 30 · 2014: 29 · 2013: 49 · 2012: 34
FWCI: 10.58
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords: leptin, lipotoxicity, lipid homeostasis, lipoapoptosis, leptin resistance, leptin deficiency, lipodystrophy, leptin receptor mutation, diet-induced obesity, type 2 diabetes, cardiomyopathy, insulin resistance, metabolic syndrome, ceramide, nitric oxide, caloric restriction, thiazolidinediones, obesity complications
MeSH terms: Adipose Tissue, Animals, Homeostasis, Humans, Lipids, Myocardium, Obesity, Risk Factors, Leptin, Metabolic Syndrome

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

Lipotoxic Diseases

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks