Muscle-Derived Angiopoietin-Like Protein 4 Is Induced by Fatty Acids via Peroxisome Proliferator–Activated Receptor (PPAR)-δ and Is of Metabolic Relevance in Humans
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OBJECTIVE: Long-chain fatty acids (LCFAs) contribute to metabolic homeostasis in part via gene regulation. This study's objective was to identify novel LCFA target genes in human skeletal muscle cells (myotubes). RESEARCH DESIGN AND METHODS: In vitro methods included culture and treatment of human myotubes and C2C12 cells, gene array analysis, real-time RT-PCR, Western blotting, ELISA, chromatin immunoprecipitation, and RNA interference. Human subjects (two cohorts) were characterized by oral glucose tolerance test, hyperinsulinemic-euglycemic clamp, magnetic resonance imaging and spectroscopy, and standard blood analyses (glucose, insulin, C-peptide, and plasma lipids). RESULTS: We show here that ANGPTL4 (encoding angiopoietin-like protein 4) represents a prominent LCFA-responsive gene in human myotubes. LCFA activated peroxisome proliferator-activated receptor (PPAR)-delta, but not PPAR-alpha or -gamma, and pharmacological activation of PPAR-delta markedly induced ANGPTL4 production and secretion. In C2C12 myocytes, knockdown of PPARD, but not of PPARG, blocked LCFA-mediated ANGPTL4 induction, and LCFA treatment resulted in PPAR-delta recruitment to the ANGPTL4 gene. In addition, pharmacological PPAR-delta activation induced LIPE (encoding hormone-sensitive lipase), and this response crucially depended on ANGPTL4, as revealed by ANGPTL4 knockdown. In a human cohort of 108 thoroughly phenotyped subjects, plasma ANGPTL4 positively correlated with fasting nonesterified fatty acids (P = 0.0036) and adipose tissue lipolysis (P = 0.0012). Moreover, in 38 myotube donors, plasma ANGPTL4 levels and adipose tissue lipolysis in vivo were reflected by basal myotube ANGPTL4 expression in vitro (P = 0.02, both). CONCLUSIONS: ANGPTL4 is produced by human myotubes in response to LCFA via PPAR-delta, and muscle-derived ANGPTL4 seems to be of systemic relevance in humans.
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In WAT, ANGPTL4 stimulates lipolysis via induction of adipose triglyceride lipase.
“In WAT, it was shown to stimulate lipolysis via induction of adipose triglyceride lipase [176,193] and to decrease the activity of LPL [178,194].”
Both FGF21 and ANGPTL4 induce WAT lipolysis.
“While both FGF21 [166] and ANGPTL4 [176,177] induce WAT lipolysis (4)”
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Cites
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Patti, 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 · see citing works
Peroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity
Wang, Y.-X., Lee, C.-H., Tiep, S., Yu, R. T., Ham, J., Kang, H., & Evans, R. M. (2003) · Cell · doi:10.1016/s0092-8674(03)00269-1 · Cited by 1,296 · see citing works
Regulation of Muscle Fiber Type and Running Endurance by PPARδ
Wang, Y.-X., Zhang, C.-L., Yu, R. T., Cho, H. K., Nelson, M. C., Bayuga-Ocampo, C. R., Ham, J., Kang, H., & Evans, R. M. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020294 · Cited by 1,089 · see citing works
Tanaka, T., Yamamoto, J., Iwasaki, S., Asaba, H., Hamura, H., Ikeda, Y., Watanabe, M., Magoori, K., Ioka, R. X., Tachibana, K., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306981100 · Cited by 832 · see citing works
Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running
Ostrowski, K., Rohde, T., Zacho, M., Asp, S., & Pedersen, B. K. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.949bp.x · Cited by 673 · see citing works
Metabolic Syndrome: A Clinical and Molecular Perspective
Moller, D. E., & Kaufman, K. D. (2004) · Annual Review of Medicine · doi:10.1146/annurev.med.56.082103.104751 · Cited by 631 · see citing works
Kersten, S., Mandard, S., Tan, N. S., Escher, P., METZGER, D., Chambon, P., Gonzalez, F. J., Desvergne, B., & Wahli, W. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004029200 · Cited by 560 · see citing works
Regulation of Plasma Triglycerides in Insulin Resistance and Diabetes
Ginsberg, H. N., Zhang, Y.-L., & Hernandez-Ono, A. (2005) · Archives of Medical Research · doi:10.1016/j.arcmed.2005.01.005 · Cited by 531 · see citing works
Motojima, K., Passilly, P., Peters, J. M., Gonzalez, F. J., & Latruffe, N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.27.16710 · Cited by 524 · see citing works
Romeo, S., Pennacchio, L. A., Fu, Y., Boerwinkle, E., Tybjaerg-Hansen, A., Hobbs, H. H., & Cohen, J. C. (2007) · Nature Genetics · doi:10.1038/ng1984 · Cited by 511 · see citing works
Peroxisome proliferator‐activated receptor δ controls muscle development and oxydative capability
Luquet, S., Lopez‐Soriano, J., Holst, D., Fredenrich, A., Melki, J., Rassoulzadegan, M., & Grimaldi, P. A. (2003) · The FASEB Journal · doi:10.1096/fj.03-0269fje · Cited by 509 · see citing works
Mandard, S., Zandbergen, F., van Straten, E., Wahli, W., Kuipers, F., Müller, M., & Kersten, S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m506519200 · Cited by 433 · see citing works
Köster, A., Chao, Y. B., Mosior, M., Ford, A., Gonzalez-DeWhitt, P. A., Hale, J. E., Li, D., Qiu, Y., Fraser, C. C., Yang, D. D., et al. (2005) · Endocrinology · doi:10.1210/en.2005-0476 · Cited by 427 · see citing works
Yoon, J. C., Chickering, T. W., Rosen, E. D., Dussault, B. J., Qin, Y., Soukas, A. A., Friedman, J. M., Holmes, W. E., & Spiegelman, B. M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.14.5343-5349.2000 · Cited by 399 · see citing works
Yoshida, K., Shimizugawa, T., Ono, M., & Furukawa, H. (2002) · Journal of Lipid Research · doi:10.1194/jlr.c200010-jlr200 · Cited by 368 · see citing works
Lee, J. S., Pinnamaneni, S. K., Eo, S. J., Cho, I. H., Pyo, J. H., Kim, C. K., Sinclair, A. J., Febbraio, M. A., & Watt, M. J. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01438.2005 · Cited by 325 · see citing works
Xu, A., Lam, M. C., Chan, K. W., Wang, Y., Zhang, J., Hoo, R. L. C., Xu, J. Y., Chen, B., Chow, W.-S., Tso, A. W. K., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408452102 · Cited by 315 · see citing works
Kim, I., Kim, H.-G., Kim, H., Kim, H.-H., Park, S. K., Uhm, C.-S., Lee, Z. H., & Koh, G. Y. (2000) · Biochemical Journal · doi:10.1042/bj3460603 · Cited by 284 · see citing works
Weigert, C., Brodbeck, K., Staiger, H., Kausch, C., Machicao, F., Häring, H. U., & Schleicher, E. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312692200 · Cited by 269 · see citing works
Mandard, S., Zandbergen, F. J., Tan, N. S., Escher, P., Patsouris, D., Köenig, W., Kleemann, R., Bakker, A. H. F., Veenman, F., Wahli, W., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403058200 · Cited by 267 · see citing works
Effects of dietary fatty acids on insulin sensitivity and secretion
Manco, M., Calvani, M., & Mingrone, G. (2004) · Diabetes Obesity and Metabolism · doi:10.1111/j.1462-8902.2004.00356.x · Cited by 201 · see citing works
Musclin, a novel skeletal muscle-derived secretory factor
Nishizawa, H., Matsuda, M., Yamada, Y., Kawai, K., Suzuki, E., Makishima, M., Kitamura, T., & Shimomura, I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400066200 · Cited by 182 · see citing works
Palmitate-Induced Interleukin-6 Expression in Human Coronary Artery Endothelial Cells
Staiger, H., Staiger, K., Stefan, N., Wahl, H. G., Machicao, F. E., Kellerer, M., & Häring, H. (2004) · Diabetes · doi:10.2337/diabetes.53.12.3209 · Cited by 169 · see citing works
Oligomerization and Regulated Proteolytic Processing of Angiopoietin-like Protein 4
Ge, H., Yang, G., Huang, L., Motola, D., Pourbahrami, T., & Li, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307583200 · Cited by 156 · see citing works
Brun, S., Carmona, M. C., Mampel, T., Viñas, O., Giralt, M., Iglesias, R., & Villarroya, F. (1999) · Diabetes · doi:10.2337/diabetes.48.6.1217 · Cited by 156 · see citing works
Differential regulation and properties of angiopoietin-like proteins 3 and 4
Ge, H., Cha, J.-Y., Gopal, H., Harp, C. T., Yu, X., Repa, J. J., & Li, C. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500005-jlr200 · Cited by 153 · see citing works
Mora, M. V., Scarfone, A., Calvani, M., Greco, A. V., & Mingrone, G. (2003) · Journal of the American College of Nutrition · doi:10.1080/07315724.2003.10719326 · Cited by 148 · see citing works
Stefan, N., Thamer, C., Staiger, H., Machicao, F. E., Machann, J., Schick, F., Venter, C., Niess, A. M., Laakso, M., Fritsche, A., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1785 · Cited by 141 · see citing works
Staiger, K., Staiger, H., Weigert, C., Haas, C., Häring, H., & Kellerer, M. (2006) · Diabetes · doi:10.2337/db06-0188 · Cited by 139 · see citing works
High Visceral Fat Mass and High Liver Fat Are Associated with Resistance to Lifestyle Intervention
Thamer, C., Machann, J., Stefan, N., Haap, M. M., Schäfer, S., Brenner, S., Kantartzis, K., Claussen, C. D., Schick, F., Häring, H. U., et al. (2007) · Obesity · doi:10.1038/oby.2007.568 · Cited by 127 · see citing works
Staiger, H., Kaltenbach, S., Staiger, K., Stefan, N., Fritsche, A., Guirguis, A., Péterfi, C., Weisser, M., Machicao, F. E., Stümvoll, M., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.9.2195 · Cited by 123 · see citing works
Dietary fats, fatty acids and insulin resistance: short review of a multifaceted connection.
Haag, M., & Dippenaar, N. (2005) · PubMed · Cited by 120 · see citing works
Oligomerization state-dependent hyperlipidemic effect of angiopoietin-like protein 4
Ge, H., Yang, G., Yu, X., Pourbahrami, T., & Li, C. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m400138-jlr200 · Cited by 115 · see citing works
Fritz, T., Kramer, D., Karlsson, H., Galuska, D., Engfeldt, P., Zierath, J. R., & Krook, A. (2006) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.656 · Cited by 114 · see citing works
Inhibition of cardiac lipoprotein utilization by transgenic overexpression of Angptl4 in the heart
Yu, X., Burgess, S. C., Ge, H., Wong, K. K., Naseem, R. H., Garry, D. J., Sherry, A. D., Malloy, C. R., Berger, J. P., & Cai, L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409564102 · Cited by 114 · see citing works
Lifestyle intervention in individuals with normal versus impaired glucose tolerance
Schäfer, S., Kantartzis, K., Machann, J., Venter, C., Niess, A. M., Schick, F., Machicao, F. E., Häring, H.-U., Fritsche, A., & Stefan, N. (2007) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2007.01820.x · Cited by 107 · see citing works
Park, K. S., Ciaraldi, T. P., Lindgren, K., Abrams-Carter, L., Mudaliar, S. R. D., Nikoulina, S. E., Tufari, S. R., Veerkamp, J. H., Vidal‐Puig, A., & Henry, R. R. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.8.5034 · Cited by 103 · see citing works
Luquet, S. H., López‐Soriano, J., Holst, D., Gaudel, C., Jehl-Piétri, C., Fredenrich, A., & Grimaldi, P. A. (2004) · Biochimie · doi:10.1016/j.biochi.2004.09.024 · Cited by 97 · see citing works
Abbot, E. L., McCormack, J. G., Reynet, C., Hassall, D. G., Buchan, K. W., & Yeaman, S. J. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.04713.x · Cited by 93 · see citing works
Krützfeldt, J., Kausch, C., Volk, A., Klein, H., Kristian, R. E. T. T., Häring, H., & Stümvoll, M. (2000) · Diabetes · doi:10.2337/diabetes.49.6.992 · Cited by 65 · see citing works
Staiger, H., Staiger, K., Haas, C., Weisser, M., Machicao, F. E., & Häring, H.-U. (2005) · Diabetologia · doi:10.1007/s00125-005-1895-z · Cited by 41 · see citing works
Kannisto, K., Chibalin, A., Glinghammar, B., Zierath, J. R., Hamsten, A., & Ehrenborg, E. (2006) · International Journal of Molecular Medicine · doi:10.3892/ijmm.17.1.45 · Cited by 36 · see citing works
Stejskal, D., Karpíšek, M., Reutová, H., Humeňanská, V., Petzel, M., Kušnierová, P., Vareka, I., Vařeková, R., & Stejskal, P. (2008) · PubMed · Cited by 33 · see citing works
Effect of genotype on success of lifestyle intervention in subjects at risk for type 2 diabetes
Weyrich, P., Stefan, N., Häring, H., Laakso, M., & Fritsche, A. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-006-0134-5 · Cited by 32 · see citing works
Staiger, H., Stefan, N., Machicao, F. E., Fritsche, A., & Häring, H. (2005) · Diabetologia · doi:10.1007/s00125-005-0061-y · Cited by 23 · see citing works
Stegall, T., & Krolick, K. A. (2000) · Clinical Immunology · doi:10.1006/clim.1999.4822 · Cited by 22 · see citing works
Stejskal, D., Karpíšek, M., Humeňanská, V., Solichová, P., & Stejskal, P. (2007) · PubMed · Cited by 19 · see citing works
Kausch, C., Staiger, H., Staiger, K., Krützfeldt, J., Matthaei, S., Häring, H.-U., & Stümvoll, M. (2003) · Hormone and Metabolic Research · doi:10.1055/s-2003-43501 · Cited by 10 · see citing works
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Ley, R. E. (2009) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e328333d751 · Cited by 760 · see citing works
Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance
Meex, R. C. R., & Watt, M. J. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.56 · Cited by 631 · see citing works
Physiological regulation of lipoprotein lipase
Kersten, S. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.03.013 · Cited by 548 · see citing works
Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations
Hoffmann, C., & Weigert, C. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029793 · Cited by 393 · see citing works
Alex, S., Lange, K., Amolo, T., Grinstead, J. S., Haakonsson, A. K., Szalowska, E., Koppen, A., Mudde, K., Haenen, D., Al-Lahham, S., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00858-12 · Cited by 300 · see citing works
Adipo-myokines: two sides of the same coin–mediators of inflammation and mediators of exercise
Raschke, S., & Eckel, J. (2013) · Mediators of Inflammation · doi:10.1155/2013/320724 · Cited by 296 · see citing works
Mechanisms of Gene Regulation by Fatty Acids
Georgiadi, A., & Kersten, S. (2012) · Advances in Nutrition · doi:10.3945/an.111.001602 · Cited by 290 · see citing works
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278 · see citing works
Angiopoietin-like 4: a decade of research
Zhu, P., Goh, Y. Y., Chin, H. F. A., Kersten, S., & Tan, N. S. (2011) · Bioscience Reports · doi:10.1042/bsr20110102 · Cited by 261 · see citing works
The influence of skeletal muscle on systemic aging and lifespan
Demontis, F., Piccirillo, R., Goldberg, A. L., & Perrimon, N. (2013) · Aging Cell · doi:10.1111/acel.12126 · Cited by 238 · see citing works
Ehrenborg, E., & Krook, A. (2009) · Pharmacological Reviews · doi:10.1124/pr.109.001560 · Cited by 213 · see citing works
Regulation of lipoprotein lipase by Angptl4
Dijk, W., & Kersten, S. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.12.005 · Cited by 199 · see citing works
Wagner, K., & Wagner, N. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.12.001 · Cited by 191 · see citing works
Raschke, S., Eckardt, K., Bjørklund Holven, K., Jensen, J., & Eckel, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062008 · Cited by 199 · see citing works
Regulation of triglyceride metabolism by Angiopoietin-like proteins
Mattijssen, F., & Kersten, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.10.010 · Cited by 180 · see citing works
Robciuc, M. R., Maranghi, M., Lahikainen, A., Rader, D. J., Bensadoun, A., Öörni, K., Metso, J., Minicocci, I., Ciociola, E., Ceci, F., et al. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301397 · Cited by 176 · see citing works
Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease
Ramanathan, R., Ali, A. H., & Ibdah, J. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137280 · Cited by 179 · see citing works
Paglia, L. L., Listì, A., Caruso, S., Amodeo, V., Passiglia, F., Bazan, V., & Fanale, D. (2017) · PPAR Research · doi:10.1155/2017/8187235 · Cited by 174 · see citing works
Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome
Clément, L. C., Macé, C., Ávila-Casado, C., Joles, J. A., Kersten, S., & Chugh, S. S. (2013) · Nature Medicine · doi:10.1038/nm.3396 · Cited by 173 · see citing works
Basu, D., Huggins, L.-A., Scerbo, D. A., Obunike, J. C., Mullick, A. E., Rothenberg, P., Prospero, N. A. D., Eckel, R. H., & Goldberg, I. J. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.311339 · Cited by 163 · see citing works
Physiological functions of peroxisome proliferator-activated receptor β
Neels, J. G., & Grimaldi, P. A. (2014) · Physiological Reviews · doi:10.1152/physrev.00027.2013 · Cited by 161 · see citing works
More than a store: regulatory roles for glycogen in skeletal muscle adaptation to exercise
Philp, A., Hargreaves, M., & Baar, K. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00004.2012 · Cited by 155 · see citing works
Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise
Catoire, M., Alex, S., Paraskevopulos, N., Mattijssen, F., Evers-van Gogh, I., Schaart, G., Jeppesen, J., Kneppers, A., Mensink, M., Voshol, P. J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400889111 · Cited by 150 · see citing works
Chen, Y., Pottanat, T. G., Siegel, R. W., Ehsani, M. E., Qian, Y., Zhen, Y., Regmi, A., Roell, W. C., Guo, H., Luo, M., et al. (2020) · Journal of Lipid Research · doi:10.1194/jlr.ra120000781 · Cited by 145 · see citing works
Role and mechanism of the action of angiopoietin-like protein ANGPTL4 in plasma lipid metabolism
Kersten, S. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100150 · Cited by 146 · see citing works
Sanderson, L. M., Degenhardt, T., Koppen, A., Kalkhoven, E., Desvergne, B., Müller, M. M., & Kersten, S. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00370-09 · Cited by 145 · see citing works
The search for exercise factors in humans
Catoire, M., & Kersten, S. (2015) · The FASEB Journal · doi:10.1096/fj.14-263699 · Cited by 137 · see citing works
Systemic Nutrient and Stress Signaling via Myokines and Myometabolites
Rai, M., & Demontis, F. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105305 · Cited by 123 · see citing works
Aryal, B., Rotllán, N., Araldi, E., Ramírez, C. M., He, S., Chousterman, B. G., Fenn, A. M., Wanschel, A. C. B. A., Madrigal‐Matute, J., Warrier, N., et al. (2016) · Nature Communications · doi:10.1038/ncomms12313 · Cited by 114 · see citing works
Down-regulation of SREBP-1c is associated with the development of burned-out NASH
Nagaya, T., Tanaka, N., Suzuki, T., Sano, K., Horiuchi, A., Komatsu, M., Nakajima, T., Nishizawa, T., Joshita, S., Umemura, T., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.04.033 · Cited by 111 · see citing works
Nikolić, N., Görgens, S. W., Thoresen, G. H., Aas, V., Eckel, J., & Eckardt, K. (2016) · Acta Physiologica · doi:10.1111/apha.12830 · Cited by 110 · see citing works
Davison, J. M., Lickwar, C. R., Song, L., Breton, G., Crawford, G. E., & Rawls, J. F. (2017) · Genome Research · doi:10.1101/gr.220111.116 · Cited by 111 · see citing works
Quantitation of serum angiopoietin-like proteins 3 and 4 in a Finnish population sample
Robciuc, M. R., Tahvanainen, E., Jauhiainen, M., & Ehnholm, C. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m002618 · Cited by 107 · see citing works
Roberts, L. D., Murray, A. J., Menassa, D. A., Ashmore, T., Nicholls, A. W., & Griffin, J. L. (2011) · Genome biology · doi:10.1186/gb-2011-12-8-r75 · Cited by 106 · see citing works
Staiger, H., Böhm, A., Scheler, M., Berti, L., Machann, J., Schick, F., Machicao, F. E., Fritsche, A., Stefan, N., Weigert, C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061903 · Cited by 105 · see citing works
Graugnard, D. E., Moyes, K. M., Trevisi, E., Khan, M. J., Keisler, D. H., Drackley, J. K., Bertoni, G., & Loor, J. J. (2012) · Journal of Dairy Science · doi:10.3168/jds.2012-5676 · Cited by 97 · see citing works
Docosahexaenoic acid stimulates tube formation in first trimester trophoblast cells, HTR8/SVneo
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Garneau, L., & Aguer, C. (2019) · Diabetes & Metabolism · doi:10.1016/j.diabet.2019.02.006 · Cited by 92 · see citing works
Angptl4 serves as an endogenous inhibitor of intestinal lipid digestion
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Ruscica, M., Zimetti, F., Adorni, M. P., Sirtori, C. R., Lupo, M. G., & Ferri, N. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104653 · Cited by 84 · see citing works
Modulation of plasma TG lipolysis by Angiopoietin-like proteins and GPIHBP1
Lichtenstein, L., & Kersten, S. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.12.015 · Cited by 78 · see citing works
Effects of the PPAR-δ agonist MBX-8025 on atherogenic dyslipidemia
Choi, Y., Roberts, B. K., Wang, X., Geaney, J. C., Naim, S., Wojnoonski, K., Karpf, D. B., & Krauss, R. M. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.10.029 · Cited by 78 · see citing works
Smart, M., Robciuc, M. R., Cooper, J. A., Jauhiainen, M., Meena Kumari, B., Mika Kivimaki, B., Khaw, K., Boekholdt, S. M., Wareham, N. J., Gaunt, T. R., et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.212209 · Cited by 75 · see citing works
Transcriptional control of physiological and pathological processes by the nuclear receptor PPARβ/δ
Tan, N. S., Vázquez‐Carrera, M., Montagner, A., Sng, M. K., Guillou, H., & Wahli, W. (2016) · Progress in Lipid Research · doi:10.1016/j.plipres.2016.09.001 · Cited by 74 · see citing works
Metabolic switching of human myotubes is improved by n-3 fatty acids
Hessvik, N. P., Bakke, S. S., Fredriksson, K., Boekschoten, M. V., Fj⊘rkenstad, A., Koster, G., Hesselink, M. K., Kersten, S., Kase, E. T., Rustan, A. C., et al. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m003319 · Cited by 71 · see citing works
Implication of hepatokines in metabolic disorders and cardiovascular diseases
Jung, T. W., Yoo, H. J., & Choi, K. M. (2016) · BBA Clinical · doi:10.1016/j.bbacli.2016.03.002 · Cited by 71 · see citing works
Fasting induces ANGPTL4 and reduces LPL activity in human adipose tissue
Ruppert, P. M. M., Michielsen, C. C. J. R., Hazebroek, E. J., Pirayesh, A., Olivecrona, G., Afman, L. A., & Kersten, S. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101033 · Cited by 69 · see citing works
Angiopoietin-like protein 4: health effects, modulating agents and structure–function relationships
Grootaert, C., de Wiele, T. V., Verstraete, W., Bracke, M., & Vanhoecke, B. W. A. (2012) · Expert Review of Proteomics · doi:10.1586/epr.12.12 · Cited by 69 · see citing works
Factors mediating exercise‐induced organ crosstalk
Sabaratnam, R., Wojtaszewski, J. F. P., & Højlund, K. (2022) · Acta Physiologica · doi:10.1111/apha.13766 · Cited by 69 · see citing works
González‐Muniesa, P., de Oliveira, C., de Heredia, F. P., Thompson, M. P., & Trayhurn, P. (2011) · Lifestyle Genomics · doi:10.1159/000327774 · Cited by 66 · see citing works
The Role of the gut Microbiome in the Pathogenesis and Treatment of Obesity
Okeke, F. C., Roland, B. C., & Mullin, G. E. (2014) · Global Advances in Health and Medicine · doi:10.7453/gahmj.2014.018 · Cited by 62 · see citing works
Ingerslev, B., Hansen, J. S., Hoffmann, C., Clemmesen, J. O., Secher, N. H., Scheler, M., Hrabĕ de Angelis, M., Häring, H. U., Pedersen, B. K., Weigert, C., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.06.018 · Cited by 61 · see citing works
Robciuc, M. R., Skrobuk, P., Anisimov, A., Olkkonen, V. M., Alitalo, K. K., Eckel, R. H., Koistinen, H. A., Jauhiainen, M., & Ehnholm, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046212 · Cited by 61 · see citing works
Sárközy, M., Zvara, Á., Gyémánt, N., Fekete, V., Kocsis, G. F., Pipis, J., Szűcs, G., Csonka, C., Puskás, L. G., Ferdinandy, P., et al. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-16 · Cited by 60 · see citing works
Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans
Laker, R. C., Garde, C., CAMERA, D. M., Smiles, W. J., Zierath, J. R., Hawley, J. A., & Barrès, R. (2017) · Scientific Reports · doi:10.1038/s41598-017-15420-7 · Cited by 58 · see citing works
Impacts of angiopoietin-like proteins on lipoprotein metabolism and cardiovascular events
Miida, T., & Hirayama, S. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328333269e · Cited by 59 · see citing works
Willecke, F., Scerbo, D. A., Nagareddy, P. R., Obunike, J. C., Barrett, T. J., Abdillahi, M., Trent, C. M., Huggins, L. A., Fisher, E. A. A., Drosatos, K., et al. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304615 · Cited by 59 · see citing works
Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities for PPARs
Yamada, H., Oshiro, E., Kikuchi, S., Hakozaki, M., Takahashi, H., & Kimura, K. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m047514 · Cited by 57 · see citing works
Effects of Angiopoietin-Like 3 on Triglyceride Regulation, Glucose Homeostasis, and Diabetes
Christopoulou, E. C., Elisaf, M., & Filippatos, T. D. (2019) · Disease Markers · doi:10.1155/2019/6578327 · Cited by 56 · see citing works
Camp, J. G., Jazwa, A. L., Trent, C. M., & Rawls, J. F. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002585 · Cited by 58 · see citing works
Takahashi, H., Kotani, K., Tanaka, K., Egucih, Y., & Anzai, K. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00588 · Cited by 55 · see citing works
Rogowski, M. P., Flowers, M. T., Stamatikos, A., Ntambi, J. M., & Paton, C. M. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m035865 · Cited by 55 · see citing works
Shen, C., Chan, S., Lee, C., Huang, W., Tsai, J.-P., & Chen, B. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.11.012 · Cited by 55 · see citing works
Role of exercise-induced hepatokines in metabolic disorders
Ennequin, G., Sirvent, P., & Whitham, M. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00433.2018 · Cited by 54 · see citing works
Regulation of angiopoietin-like protein 4 production during and after exercise
Norheim, F., Hjorth, M., Langleite, T. M., Lee, S., Holen, T., Bindesbøll, C., Stadheim, H. K., Gulseth, H. L., Birkeland, K. I., Kielland, A., et al. (2014) · Physiological Reports · doi:10.14814/phy2.12109 · Cited by 53 · see citing works
Lysophosphatidylcholines activate PPARδ and protect human skeletal muscle cells from lipotoxicity
Klingler, C., Zhao, X., Adhikary, T., Li, J., Xu, G., Häring, H., Schleicher, E. D., Lehmann, R., & Weigert, C. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.09.020 · Cited by 53 · see citing works
Vascular PPARβ/δ Promotes Tumor Angiogenesis and Progression
Wagner, K., Du, S., Martin, L., Cardot‐Leccia, N., Michiels, J., & Wagner, N. (2019) · Cells · doi:10.3390/cells8121623 · Cited by 53 · see citing works
Angiopoietin-like 4 based therapeutics for proteinuria and kidney disease
Chugh, S. S., Macé, C., Clément, L. C., Avila, M. D. N., & Marshall, C. B. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00023 · Cited by 52 · see citing works
Poplawski, M. M., Mastaitis, J. W., Yang, X.-J., & Mobbs, C. V. (2010) · Endocrinology · doi:10.1210/en.2010-0702 · Cited by 49 · see citing works
α1-Antitrypsin Combines with Plasma Fatty Acids and Induces Angiopoietin-like Protein 4 Expression
Frenzel, E., Wrenger, S., Brügger, B., Salipalli, S., Immenschuh, S., Aggarwal, N., Lichtinghagen, R., Mahadeva, R., Marcondes, A. M., Dinarello, C. A., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500740 · Cited by 47 · see citing works
Zhu, C., Zhou, W., Han, M., Yang, Y., Li, Y., Jiang, Q., & Lv, W. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.164460 · Cited by 46 · see citing works
Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism
Lund, J., Rustan, A. C., Løvsletten, N. G., Mudry, J. M., Langleite, T. M., Feng, Y., Stensrud, C., Brubak, M. G., Drevon, C. A., Birkeland, K. I., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175441 · Cited by 43 · see citing works
Barja-Fernández, S., Moreno‐Navarrete, J. M., Folgueira, C., Xifra, G., Sabater, M., Castelao, C., Fernø, J., Leis, R., Diéguez, C., Casanueva, F. F., et al. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800060 · Cited by 43 · see citing works
Zamboni, M. M., Mazzali, G., Brunelli, A., Saatchi, T., Urbani, S., Giani, A., Rossi, A. P., Zoico, E., & Fantin, F. (2022) · Cells · doi:10.3390/cells11213361 · Cited by 42 · see citing works
Ruge, T., Sukonina, V., Kroupa, O., Makoveichuk, E., Lundgren, M., Svensson, M. K. E., Olivecrona, G., & Eriksson, J. W. (2011) · Metabolism · doi:10.1016/j.metabol.2011.09.014 · Cited by 42 · see citing works
A review of the multifunctionality of angiopoietin-like 4 in eye disease
Yang, X., Cheng, Y., & Su, G. (2018) · Bioscience Reports · doi:10.1042/bsr20180557 · Cited by 42 · see citing works
Zizola, C. F., Kennel, P. J., Akashi, H., Ji, R., Castillero, E., George, I., Homma, S., & Schulze, P. C. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00679.2014 · Cited by 39 · see citing works
Lipoprotein Lipase and Its Delivery of Fatty Acids to the Heart
Shang, R., & Rodrigues, B. B. (2021) · Biomolecules · doi:10.3390/biom11071016 · Cited by 38 · see citing works
Chellan, B., Rojas, E., Zhang, C., & Bowman, M. A. H. (2018) · Scientific Reports · doi:10.1038/s41598-018-30073-w · Cited by 37 · see citing works
Makoveichuk, E., Sukonina, V., Kroupa, O., Thulin, P., Ehrenborg, E., Olivecrona, T., & Olivecrona, G. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.07.048 · Cited by 37 · see citing works
Liu, S.-H., Cai, F.-Y., & Chiang, M.-T. (2015) · Marine Drugs · doi:10.3390/md13127067 · Cited by 34 · see citing works
Wang, Y., Puthanveetil, P., Wang, F., Kim, M. S., Abrahani, A., & Rodrigues, B. B. (2011) · Diabetes · doi:10.2337/db11-0042 · Cited by 36 · see citing works
Insulin resistance and metabolic flexibility as drivers of liver and cardiac disease in T2DM
Colosimo, S., Mitra, S. K., Chaudhury, T., & Marchesini, G. (2023) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2023.111016 · Cited by 38 · see citing works
Hepatokines as a Molecular Transducer of Exercise
Seo, D. Y., Park, S.-H., Marquez, J. C., Kwak, H., Kim, T. N., Bae, J. H., Koh, J., & Han, J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10030385 · Cited by 36 · see citing works
Robal, T., Larsson, M., Martin, M., Olivecrona, G., & Lõokene, A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.303529 · Cited by 33 · see citing works
Feng, Y. Z., Nikolić, N., Bakke, S. S., Boekschoten, M. V., Kersten, S., Kase, E. T., Rustan, A. C., & Thoresen, G. H. (2013) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2013.829105 · Cited by 32 · see citing works
Metabolic and nonmetabolic regulatory functions of peroxisome proliferator-activated receptor β
Grimaldi, P. A. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32833884a4 · Cited by 30 · see citing works
Omega-3 long-chain fatty acids strongly induce angiopoietin-like 4 in humans
Brands, M., Sauerwein, H. P., Ackermans, M. T., Kersten, S., & Serlie, M. J. M. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m030049 · Cited by 29 · see citing works
Ordelheide, A., Gommer, N., Böhm, A., Hermann, C., Thielker, I., Machicao, F. E., Fritsche, A., Stefan, N., Häring, H., & Staiger, H. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.02.001 · Cited by 28 · see citing works
Short-Chain Fatty Acid Production and Functional Aspects on Host Metabolism
Tungland, B. C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-814649-1.00002-8 · Cited by 28 · see citing works
Yang, H. J., Xiao, L., & Xu, D. (2020) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-020-07001-0 · Cited by 26 · see citing works
PPARαIs Required for PPARδAction in Regulation of Body Weight and Hepatic Steatosis in Mice
Garbacz, W. G., Huang, J. T.-J., Higgins, L. G., Wahli, W., & Palmer, C. N. A. (2015) · PPAR Research · doi:10.1155/2015/927057 · Cited by 26 · see citing works
Chasseigneaux, S., Cochois, V., Lecorgne, L., Lochus, M., Nicolic, S., Blugeon, C., Jourdren, L., Gomez‐Zepeda, D., Tenzer, S., Sanquer, S., et al. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00526-8 · Cited by 25 · see citing works
Glaser, K., Dickie, P., Neilson, D., Osborn, A. J., & Dickie, B. (2018) · Lymphatic Research and Biology · doi:10.1089/lrb.2017.0033 · Cited by 25 · see citing works
The Emerging Role of PPAR Beta/Delta in Tumor Angiogenesis
Du, S., Wagner, N., & Wagner, K. (2020) · PPAR Research · doi:10.1155/2020/3608315 · Cited by 25 · see citing works
Frenzel, E., Wrenger, S., Immenschuh, S., Koczulla, A. R., Mahadeva, R., Deeg, H. J., Dinarello, C. A., Welte, T., Marcondes, A. M., & Janciauskiene, S. M. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400378 · Cited by 25 · see citing works
Liu, S., He, S.-P., & Chiang, M. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf300792b · Cited by 25 · see citing works
McTavish, P. V., & Mutch, D. M. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02376-7 · Cited by 24 · see citing works
Binding and activity of bisphenol analogues to human peroxisome proliferator-activated receptor β/δ
Li, C.-H., Zhang, D., Jiang, L., Qi, Y., & Guo, L. (2021) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2021.112849 · Cited by 24 · see citing works
ANGPTL4, IL-6 and TNF-α as regulators of lipid metabolism during a marathon run
Górecka, M., Krzeminski, K., Mikulski, T., & Ziemba, A. W. (2022) · Scientific Reports · doi:10.1038/s41598-022-17439-x · Cited by 24 · see citing works
- Authors
- Staiger, H., Haas, C., Machann, J., Werner, R., Weisser, M., Schick, F., Machicao, F., Stefan, N., Fritsche, A., & Häring, H.-U.
- Affiliations
- University of Tübingen (DE)
- Department of Experimental Radiology, Eberhard-Karls-University Tübingen, Tübingen, Germany
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany
- Corresponding author
- Staiger, Harald
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2009-03-01
- Volume
- 58
- Issue
- 3
- Pages
- 579-589
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2646056
- OpenAlex
- W2127054137
- Cited by
- 183
- References
- 49
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 11 · 2023: 5 · 2022: 7 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 11 · 2017: 12 · 2016: 12 · 2015: 10 · 2014: 15 · 2013: 17 · 2012: 15
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (KFO 114/1, KFO 114/1-2, KFO 114)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- ANGPTL4, long-chain fatty acids, PPARδ, skeletal muscle, myotubes, hormone-sensitive lipase, LIPE, adipose tissue lipolysis, free fatty acids, lipoprotein lipase inhibition
- MeSH terms
- Angiopoietin-Like Protein 4, Blood Glucose, C-Peptide, Gene Expression Regulation, Glucose Tolerance Test, Humans, Insulin, Lipids, RNA, Messenger, Glucose Clamp Technique, Muscle, Skeletal, Muscle Fibers, Skeletal, Palmitic Acid, Linoleic Acid, Oligonucleotide Array Sequence Analysis, Angiopoietins, PPAR alpha, PPAR delta
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