Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin
Open accessAbstract
The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival. No unifying mechanism has yet explained how adiponectin can exert such a variety of beneficial systemic effects. Here, we show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, AdipoR1 and AdipoR2, and enhances ceramide catabolism and formation of its antiapoptotic metabolite--sphingosine-1-phosphate (S1P)--independently of AMP-dependent kinase (AMPK). Using models of inducible apoptosis in pancreatic beta cells and cardiomyocytes, we show that transgenic overproduction of adiponectin decreases caspase-8-mediated death, whereas genetic ablation of adiponectin enhances apoptosis in vivo through a sphingolipid-mediated pathway. Ceramidase activity is impaired in cells lacking both adiponectin receptor isoforms, leading to elevated ceramide levels and enhanced susceptibility to palmitate-induced cell death. Combined, our observations suggest a unifying mechanism of action for the beneficial systemic effects exerted by adiponectin, with sphingolipid metabolism as its core upstream signaling component.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Adiponectin has antidiabetic effects and antagonizes the progression of DCM by exhibiting potent anti-hypertrophic activity in cardiomyocytes and diminishing cardiac cell death by inhibiting inflammation.
“Adiponectin has antidiabetic effects and antagonizes the progression of DCM by exhibiting potent anti-hypertrophic activity in cardiomyocytes and diminishing cardiac cell death by inhibiting inflammation [36-38].”
From Role of Serum Biomarkers in Early Detection of Diabetic Cardiomyopathy in the West Virginian Population (2016) · cites this paper as [37]
The Results section ('Anti-apoptotic effects of adiponectin on cardiac myocytes'; page unavailable) reports improved cardiomyocyte survival with adiponectin, and the Discussion links adiponectin to improved metabolic health. But the paper does not establish that it slows diabetic cardiomyopathy or prevents cardiac cell death by inhibiting inflammation. Contrary to the claimed anti-hypertrophic activity, the Results report cardiac hypertrophy in 20- and 30-week-old adiponectin-transgenic mice. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn peripheral tissues, adiponectin promotes liver insulin sensitivity via several independent mechanisms: an AMPK-dependent mechanism involving increased ACC phosphorylation, an AMPK-independent mechanism involving reduction in liver ceramide levels, and an IL-6-dependent mechanism involving upregulation of IRS-2 through STAT3 activation.
“In the peripheral tissues, adiponectin promotes liver insulin sensitivity via several independent mechanisms: an AMPK‐dependent mechanism involving increased ACC phosphorylation, an AMPK‐independent mechanism that involves a reduction in liver ceramide levels 57, and an IL‐6‐dependent mechanism that involves the upregulation of insulin receptor substrate 2 (IRS‐2) through the activation of STAT3 5”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [57]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238 · see citing works
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., et al. (2003) · Nature · doi:10.1038/nature01705 · Cited by 3,176 · see citing works
The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
Berg, A. H., Combs, T. P., Du, X., Brownlee, M., & Scherer, P. E. (2001) · Nature Medicine · doi:10.1038/90992 · Cited by 2,526 · see citing works
Self-citationSphingosine-1-phosphate: an enigmatic signalling lipid
Spiegel, S., & Milstien, S. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1103 · Cited by 2,080 · see citing works
Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797 · see citing works
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
Yamauchi, T., Nio, Y., Maki, T., Kobayashi, M., Takazawa, T., Iwabu, M., Okada-Iwabu, M., Kawamoto, S., Kubota, N., Kubota, T., et al. (2007) · Nature Medicine · doi:10.1038/nm1557 · Cited by 1,396 · see citing works
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-citationHolland, W. L., Brozinick, J. T., Wang, L.-P., Hawkins, E. D., Sargent, K. M., Liu, Y., Narra, K., Hoehn, K. L., Knotts, T. A., Siesky, A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.01.002 · Cited by 1,232 · see citing works
Self-citationDisruption of Adiponectin Causes Insulin Resistance and Neointimal Formation
Kubota, N., Terauchi, Y., Yamauchi, T., Kubota, T., Moroi, M., Matsui, J., Eto, K., Yamashita, T., Kamon, J., Satoh, H., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200251200 · Cited by 1,213 · see citing works
Disruption of adiponectin causes insulin resistance and neointimal formation
Froguel, P. (2002) · HAL · Cited by 1,126 · see citing works
Disordered lipid metabolism and the pathogenesis of insulin resistance.
Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007) · Physiological Reviews · doi:10.1152/physrev.00024.2006 · Cited by 1,107 · see citing works
Structure-Function Studies of the Adipocyte-secreted Hormone Acrp30/Adiponectin
Pajvani, U. B., Du, X., Combs, T. P., Berg, A. H., Rajala, M. W., Schulthess, T., Engel, J., Brownlee, M., & Scherer, P. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m207198200 · Cited by 1,090 · see citing works
Self-citationAdiponectin and AdipoR1 Regulate PGC-1α and Mitochondria by Ca2+ and AMPK/SIRT1
Iwabu, M., Yamauchi, T., Okada-Iwabu, M., Sato, K., Nakagawa, T., Funata, M., Yamaguchi, M., Namiki, S., Nakayama, R., Tabata, M., et al. (2010) · Nature · doi:10.1038/nature08991 · Cited by 971 · see citing works
Endogenous glucose production is inhibited by the adipose-derived protein Acrp30
Combs, T. P., Berg, A. H., Obici, S., Scherer, P. E., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14120 · Cited by 935 · see citing works
Self-citationMu, J., Brozinick, J. T., Valladares, O., Bucan, M., & Birnbaum, M. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00251-9 · Cited by 924 · see citing works
Self-citationHohmeier, H. E., Mulder, H., Chen, G., Henkel-Rieger, R., Prentki, M., & Newgard, C. B. (2000) · Diabetes · doi:10.2337/diabetes.49.3.424 · Cited by 922 · see citing works
A mechanistic role for cardiac myocyte apoptosis in heart failure
Wencker, D., Chandra, M., Nguyen, K., Miao, W., Garantziotis, S., Factor, S. M., Shirani, J., Armstrong, R. C., & Kitsis, R. N. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17664 · Cited by 765 · see citing works
“Inside-Out” Signaling of Sphingosine-1-Phosphate: Therapeutic Targets
Takabe, K., Paugh, S. W., Milstien, S., & Spiegel, S. (2008) · Pharmacological Reviews · doi:10.1124/pr.107.07113 · Cited by 719 · see citing works
AMPK: a key regulator of energy balance in the single cell and the whole organism
Hardie, D. G. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.116 · Cited by 705 · see citing works
Nawrocki, A. R., Rajala, M. W., Tomás, E., Pajvani, U. B., Saha, A. K., Trumbauer, M. E., Pang, Z., Chen, A. S., Ruderman, N. B., Chen, H., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505311200 · Cited by 640 · see citing works
Self-citationDe Novo Sphingolipid Biosynthesis: A Necessary, but Dangerous, Pathway
Merrill, A. H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.r200009200 · Cited by 618 · see citing works
Holland, W. L., & Summers, S. A. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0025 · Cited by 594 · see citing works
Self-citationRedesigning an FKBP–ligand interface to generate chemical dimerizers with novel specificity
Clackson, T., Yang, W., Rozamus, L. W., Hatada, M., Amara, J. F., Rollins, C. T., Stevenson, L. F., Magari, S. R., Wood, S. A., Courage, N. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10437 · Cited by 558 · see citing works
Combs, T. P., Pajvani, U. B., Berg, A. H., Lin, Y., Jelicks, L. A., Laplante, M., Nawrocki, A. R., Rajala, M. W., Parlow, A. F., Cheeseboro, L., et al. (2004) · Endocrinology · doi:10.1210/en.2003-1068 · Cited by 545 · see citing works
Self-citationEnhanced insulin sensitivity in mice lacking ganglioside GM3
Yamashita, T., Hashiramoto, A., Haluzik, M., Mizukami, H., Beck, S., Norton, A., Kono, M., Tsuji, S., Daniotti, J. L., Werth, N., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0635898100 · Cited by 531 · see citing works
PKC-θ knockout mice are protected from fat-induced insulin resistance
Kim, J. K., Fillmore, J. J., Sunshine, M. J., Albrecht, B., Higashimori, T., Kim, D.-W., Liu, Z.-X., Soos, T. J., Cline, G. W., O’Brien, W. R., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422230 · Cited by 500 · see citing works
Regulation of Insulin Action by Ceramide
Stratford, S., Hoehn, K. L., Liu, F., & Summers, S. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406499200 · Cited by 410 · see citing works
Self-citationMao, C. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2008.06.002 · Cited by 399 · see citing works
Powell, D. J., Hajduch, É., Kular, G. S., & Hundal, H. S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7794-7808.2003 · Cited by 371 · see citing works
Stein, D. T., Stevenson, B. E., Chester, M. W., Basit, M., Daniels, M. B., Turley, S. D., & McGarry, J. D. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119546 · Cited by 352 · see citing works
Benoit, S. C., Kemp, C. J., Elias, C. F., Abplanalp, W., Herman, J. P., Migrenne, S., Lefevre, A.-L., Cruciani-Guglielmacci, C., Magnan, C., Yu, F., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36714 · Cited by 351 · see citing works
Self-citationPajvani, U. B., Trujillo, M. E., Combs, T. P., Iyengar, P., Jelicks, L., Roth, K. A., Kitsis, R. N., & Scherer, P. E. (2005) · Nature Medicine · doi:10.1038/nm1262 · Cited by 322 · see citing works
Self-citationPharmacological Inhibition of Glucosylceramide Synthase Enhances Insulin Sensitivity
Aerts, J. M. F. G., Ottenhoff, R., Powlson, A., Grefhorst, A., van Eijk, M., Dubbelhuis, P. F., Aten, J., Kuipers, F., Serlie, M. J. M., Wennekes, T., et al. (2007) · Diabetes · doi:10.2337/db06-1619 · Cited by 301 · see citing works
Berglund, E. D., Li, C. Y., Bina, H. A., Lynes, S. E., Michael, M. D., Shanafelt, A. B., Kharitonenkov, A., & Wasserman, D. H. (2009) · Endocrinology · doi:10.1210/en.2009-0221 · Cited by 297 · see citing works
Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-α
Puigserver, P. (2005) · International Journal of Obesity · doi:10.1038/sj.ijo.0802905 · Cited by 290 · see citing works
Zhao, H., Przybylska, M., Wu, I., Zhang, J., Siegel, C., Komarnitsky, S., Yew, N. S., & Cheng, S. H. (2007) · Diabetes · doi:10.2337/db06-0719 · Cited by 238 · see citing works
Plasma Adiponectin Complexes Have Distinct Biochemical Characteristics
Schraw, T., Wang, Z. V., Halberg, N., Hawkins, M. A., & Scherer, P. E. (2008) · Endocrinology · doi:10.1210/en.2007-1561 · Cited by 216 · see citing works
Self-citationMukhopadhyay, A., Saddoughi, S. A., Song, P., Sultan, I. Y., Ponnusamy, S., Senkal, C. E., Snook, C. F., Arnold, H., Sears, R. C., Hanniui, Y. A., et al. (2008) · The FASEB Journal · doi:10.1096/fj.08-120550 · Cited by 208 · see citing works
Agonist-modulated Regulation of AMP-activated Protein Kinase (AMPK) in Endothelial Cells
Levine, Y. C., Li, G. K., & Michel, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702182200 · Cited by 207 · see citing works
Olivera, A., Mizugishi, K., Tikhonova, A., Ciaccia, L., Odom, S., Proia, R. L., & Rivera, J. (2007) · Immunity · doi:10.1016/j.immuni.2007.02.008 · Cited by 206 · see citing works
Systemic Fate of the Adipocyte-Derived Factor Adiponectin
Halberg, N., Schraw, T., Wang, Z. V., Kim, J., Yi, J., Hamilton, M. P., Luby‐Phelps, K., & Scherer, P. E. (2009) · Diabetes · doi:10.2337/db08-1750 · Cited by 198 · see citing works
Self-citationCeramide Recruits and Activates Protein Kinase C ζ (PKCζ) within Structured Membrane Microdomains
Fox, T. E., Houck, K. L., O'Neill, S. M., Nagarajan, M., Stover, T. C., Pomianowski, P. T., Unal, O., Yun, J. K., Naides, S. J., & KESTER, M. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700082200 · Cited by 185 · see citing works
The Role of AMPK and mTOR in Nutrient Sensing in Pancreatic β-Cells
Gleason, C. E., Lu, D., Witters, L. A., Newgard, C. B., & Birnbaum, M. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610631200 · Cited by 179 · see citing works
Self-citationCloning and Characterization of a Novel Human Alkaline Ceramidase
Mao, C., Xu, R., Szulc, Z. M., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102818200 · Cited by 163 · see citing works
Enhanced metabolic flexibility associated with elevated adiponectin levels
Asterholm, I. W., & Scherer, P. E. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.090647 · Cited by 157 · see citing works
Self-citationBurger, D. E., Lei, M., Geoghegan-Morphet, N., Lü, X., Xenocostas, A., & Feng, Q. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.06.026 · Cited by 152 · see citing works
Veldhoven, P. P. V., Gijsbers, S., Mannaerts, G. P., et al. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(00)00079-2 · Cited by 111 · see citing works
Sphingosine Is a Novel Activator of 3-Phosphoinositide-dependent Kinase 1
King, C. C., Zenke, F. T., Dawson, P. E., Sonnenburg, E. D., Newton, A. C., Hemmings, B. A., & Bokoch, G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m909663199 · Cited by 103 · see citing works
Sphingolipids Function as Downstream Effectors of a Fungal PAQR
Villa, N., Kupchak, B. R., Garitaonandia, I., et al. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.049809 · Cited by 87 · see citing works
Quantitative Determination of Ceramide Using Diglyceride Kinase
Perry, D. K., Bielawska, A. E., & Hannun, Y. A. (2000) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(00)12897-6 · Cited by 85 · see citing works
Evidence for a role of sphingosine-1 phosphate in cardiovascular remodelling in Fabry disease
Brakch, N., Dormond, O., Bekri, S., et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp387 · Cited by 83 · see citing works
Inflammatory mechanisms in diabetes: lessons from the β-cell
Hohmeier, H. E., Tran, V. V., Chen, G., Gasa, R., & Newgard, C. B. (2003) · International Journal of Obesity · doi:10.1038/sj.ijo.0802493 · Cited by 68 · see citing works
PANIC-ATTAC: A Mouse Model for Inducible and Reversible β-Cell Ablation
Wang, Z. V., Mu, J., Schraw, T., Gautron, L., Elmquist, J. K., Zhang, B. B., Brownlee, M., & Scherer, P. E. (2008) · Diabetes · doi:10.2337/db07-1631 · Cited by 66 · see citing works
Self-citationInhibitory actions of ceramide upon PKC-ε/ERK interactions
Bourbon, N. A., Yun, J. K., Berkey, D., Wang, Y., & KESTER, M. A. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.280.6.c1403 · Cited by 65 · see citing works
Sphingosine Kinase and Sphingosine 1-Phosphate in Cardioprotection
Karliner, J. S. (2009) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181926706 · Cited by 65 · see citing works
Li, Z., Li, Y., Chakraborty, M., Fan, Y., Bui, H. H., Peake, D. A., Kuo, M., Xiao, X., Cao, G., & Jiang, X.-C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.042028 · Cited by 45 · see citing works
Self-citationHe, L., & Fox, M. H. (1997) · Experimental Cell Research · doi:10.1006/excr.1997.3494 · Cited by 38 · see citing works
Substrate specificity of rat brain ceramidase
Bawab, S. E., Usta, J. A., Roddy, P. L., et al. (2002) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)30197-8 · Cited by 33 · see citing works
PAQRs: A Counteracting Force to Ceramides?
Holland, W. L., & Scherer, P. E. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.054817 · Cited by 30 · see citing works
Self-citationProbing the mechanism of FET3 repression by Izh2p overexpression
Kupchak, B. R., Garitaonandia, I., Villa, N., Mullen, M. B., Weaver, M. G., Regalla, L. M., Kendall, E. A., & Lyons, T. J. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2007.04.003 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016) · Metabolism · doi:10.1016/j.metabol.2015.12.012 · Cited by 3,119 · see citing works
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
Inflammatory links between obesity and metabolic disease
Lumeng, C. N., & Saltiel, A. R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57132 · Cited by 2,319 · see citing works
Stern, J. H., Rutkowski, J. M., & Scherer, P. E. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.011 · Cited by 1,031 · see citing works
Self-citationWhy does obesity cause diabetes?
Klein, S., Gastaldelli, A., Yki-Järvinen, H., & Scherer, P. E. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.012 · Cited by 939 · see citing works
Self-citationObesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments
Ruze, R., Liu, T., Zou, X., Song, J., Chen, Y., Xu, R., Yin, X., & Xu, Q. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1161521 · Cited by 799 · see citing works
Adipocytokines in Obesity and Metabolic Disease
Cao, H. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0339 · Cited by 705 · see citing works
Targeting adipose tissue in the treatment of obesity-associated diabetes
Kusminski, C. M., Bickel, P. E., & Scherer, P. E. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.75 · Cited by 678 · see citing works
Self-citationAdiponectin regulation and function
Fang, H., & Judd, R. L. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170046 · Cited by 631 · see citing works
Adiponectin, the past two decades
Wang, Z. V., & Scherer, P. E. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw011 · Cited by 609 · see citing works
Self-citationThe cell biology of fat expansion
Rutkowski, J. M., Stern, J. H., & Scherer, P. E. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201409063 · Cited by 541 · see citing works
Self-citationImpaired adipogenesis and dysfunctional adipose tissue in human hypertrophic obesity
Hammarstedt, A., Gogg, S., Hedjazifar, S., Nerstedt, A., & Smith, U. (2018) · Physiological Reviews · doi:10.1152/physrev.00034.2017 · Cited by 462 · see citing works
Adiponectin signaling and function in insulin target tissues
Ruan, H., & Dong, L. Q. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw014 · Cited by 395 · 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
Apostolopoulou, M., Gordillo, R., Koliaki, C., Gancheva, S., Jelenik, T., De Filippo, E., Herder, C., Markgraf, D., Jankowiak, F., Esposito, I., et al. (2018) · Diabetes Care · doi:10.2337/dc17-1318 · Cited by 284 · see citing works
Self-citationBo, T., Gao, L., Yao, Z., Shao, S., Wang, X., Proud, C. G., & Zhao, J. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.04.006 · Cited by 293 · see citing works
AMP-activated protein kinase regulation and biological actions in the heart
Zaha, V. G., & Young, L. H. (2012) · Circulation Research · doi:10.1161/circresaha.111.255505 · Cited by 279 · see citing works
Lan, T., Morgan, D. A., Rahmouni, K., Sonoda, J., Fu, X., Burgess, S. C., Holland, W. L., Kliewer, S. A., & Mangelsdorf, D. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.005 · Cited by 261 · see citing works
Self-citationAdiponectin, driver or passenger on the road to insulin sensitivity?
Ye, R., & Scherer, P. E. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.04.001 · Cited by 251 · see citing works
Self-citationRole of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases
Nakagawa, Y., & Chiba, K. (2014) · Pharmaceuticals · doi:10.3390/ph7121028 · Cited by 215 · see citing works
Diabetes and beta cell function: from mechanisms to evaluation and clinical implications
Cernea, S., & Dobreanu, M. (2013) · Biochemia Medica · doi:10.11613/bm.2013.033 · Cited by 203 · see citing works
Immunologic and endocrine functions of adipose tissue: implications for kidney disease
Zhu, Q., & Scherer, P. E. (2018) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.157 · Cited by 200 · see citing works
Self-citationInter‐organ communication: a gatekeeper for metabolic health
Castillo‐Armengol, J., Fajas, L., & Lopez‐Mejia, I. C. (2019) · The EMBO Reports · doi:10.15252/embr.201947903 · Cited by 178 · see citing works
Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes?
Valenti, L., Bugianesi, E., Pajvani, U., & Targher, G. (2016) · Liver International · doi:10.1111/liv.13185 · Cited by 171 · see citing works
Bazan, N. G. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.09.003 · Cited by 148 · see citing works
Scherer, P. E. (2016) · Diabetes · doi:10.2337/db16-0339 · Cited by 133 · see citing works
Self-citationLiver-derived systemic factors drive β cell hyperplasia in insulin-resistant states
El Ouaamari, A., Kawamori, D., Dirice, E., Liew, C. W., Shadrach, J. L., Hu, J., Katsuta, H., Hollister-Lock, J., Qian, W.-J., Wagers, A. J., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.007 · Cited by 136 · see citing works
Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival
Rice, D. S., Calandria, J. M., Gordon, W. C., Jun, B., Zhou, Y., Gelfman, C. M., Li, S., Jin, M., Knott, E. J., Chang, B., et al. (2015) · Nature Communications · doi:10.1038/ncomms7228 · Cited by 124 · see citing works
Wang, Y., Wang, X., Lau, W. B., Yuan, Y., Booth, D., Li, J.-J., Scalia, R., Preston, K., Gao, E., Koch, W., et al. (2014) · Circulation Research · doi:10.1161/circresaha.114.302439 · Cited by 104 · see citing works
Adiponectin resistance in skeletal muscle: Pathophysiological implications in chronic heart failure
Sente, T., Van Berendoncks, A. M., Hoymans, V. Y., & Vrints, C. J. (2016) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12086 · Cited by 95 · see citing works
Sphingolipids: agents provocateurs in the pathogenesis of insulin resistance
Lipina, C., & Hundal, H. S. (2011) · Diabetologia · doi:10.1007/s00125-011-2127-3 · Cited by 83 · see citing works
Ahmad, A., Ali, T., Kim, M. W., Khan, A., Jo, M. H., Rehman, S. U., Khan, M. S., Abid, N. B., Khan, M., Ullah, R., et al. (2019) · Metabolism · doi:10.1016/j.metabol.2018.10.004 · Cited by 76 · see citing works
Liu, Y., Vu, V., & Sweeney, G. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00842 · Cited by 69 · see citing works
A mutation in ADIPOR1 causes nonsyndromic autosomal dominant retinitis pigmentosa
Zhang, J., Wang, C., Shen, Y., Chen, N., Wang, L., Liang, L., Guo, T., Yin, X., Ma, Z., Zhang, B., et al. (2016) · Human Genetics · doi:10.1007/s00439-016-1730-2 · Cited by 57 · see citing works
Self-citationShaver, A., Nichols, A., Thompson, E., Mallick, A., Payne, K., Jones, C., Manne, N. D. P. K., Sundaram, S., Shapiro, J. I., & Sodhi, K. (2016) · International Journal of Medical Sciences · doi:10.7150/ijms.14141 · Cited by 54 · see citing works
Involvement of adiponectin in the pathogenesis of dystrophinopathy
Abou-Samra, M., Lecompte, S., Schakman, O., Noel, L., Many, M. C., Gailly, P., & Brichard, S. M. (2015) · Skeletal Muscle · doi:10.1186/s13395-015-0051-9 · Cited by 55 · see citing works
Effect of pioglitazone on plasma ceramides in adults with metabolic syndrome
Warshauer, J. T., Lopez, X., Gordillo, R., Hicks, J., Holland, W. L., Anuwe, E., Blankfard, M. B., Scherer, P. E., & Lingvay, I. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2662 · Cited by 51 · see citing works
Self-citationAdiponectin signaling and its role in bone metabolism
Pal China, S., Sanyal, S., & Chattopadhyay, N. (2018) · Cytokine · doi:10.1016/j.cyto.2018.06.012 · Cited by 53 · see citing works
GLP‐1 receptor agonists: effects on the progression of non‐alcoholic fatty liver disease
Liu, J., Wang, G., Jia, Y., & Xu, Y. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2580 · Cited by 48 · see citing works
Loss of transcriptional repression by BCL6 confers insulin sensitivity in the setting of obesity
Senagolage, M. D., Sommars, M. A., Ramachandran, K., Futtner, C. R., Omura, Y., Allred, A. L., Wang, J., Yang, C., Procissi, D., Evans, R. M., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.074 · Cited by 44 · see citing works
Abulizi, A., Perry, R. J., Camporez, J. P. G., Jurczak, M. J., Petersen, K. F., Aspichueta, P., & Shulman, G. I. (2017) · The FASEB Journal · doi:10.1096/fj.201700001r · Cited by 41 · see citing works
Singh, A. K., Joharapurkar, A. A., Khan, M. P., Mishra, J. S., Singh, N., Yadav, M., Hossain, Z., Khan, K., Kumar, S., Dhanesha, N. A., et al. (2014) · Diabetes · doi:10.2337/db13-1619 · Cited by 43 · see citing works
Adipokines in healthy skeletal muscle and metabolic disease
Coles, C. A. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-27511-6_6 · Cited by 39 · see citing works
Ma, Y., Nenkov, M., Chen, Y., & Gaßler, N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158352 · Cited by 28 · see citing works
Gamberi, T., Magherini, F., & Fiaschi, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071544 · Cited by 18 · see citing works
- Authors
- Holland, W. L., Miller, R. A., Wang, Z. V., Sun, K., Barth, B. M., Bui, H. H., Davis, K. E., Bikman, B. T., Halberg, N., Rutkowski, J. M., Wade, M. R., Tenorio, V. M., Kuo, M.-S., Brozinick, J. T., Zhang, B. B., Birnbaum, M. J., Summers, S. A., & Scherer, P. E.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Pennsylvania (US)
- Colorado State University (US)
- Eli Lilly (United States) (US)
- National University of Singapore (SG)
- University of Copenhagen (DK)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Scherer, Philipp E
- ORCID
- Venue
- Nature Medicine
- Published
- 2010-12-26
- Volume
- 17
- Issue
- 1
- Pages
- 55-63
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC3134999
- OpenAlex
- W2032919119
- Cited by
- 892
- References
- 61
- Citations by year
- 2026: 25 · 2025: 27 · 2024: 50 · 2023: 50 · 2022: 55 · 2021: 60 · 2020: 56 · 2019: 69 · 2018: 59 · 2017: 57 · 2016: 70 · 2015: 53 · 2014: 64 · 2013: 83 · 2012: 71
- FWCI
- 25.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- National University of Singapore (submittedVersion)
- Funders
- University of Texas Southwestern Medical Center
- National Institutes of Health (1tl1dk081181-01, 5f32dk085935-02)
- National Heart, Lung, and Blood Institute (T32HL007360)
- National Cancer Institute (R01CA112023)
- National Institute of Diabetes and Digestive and Kidney Diseases (TL1-DK081181, R01 DK 55758, P01-DK49210, R01-DK56886, F32-DK085935, R01DK056886, R01DK055758, P01DK049210, RC1DK086629, R01DK081456, F32DK081279, P01DK088761, R21DK073181, F32DK083866)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- adiponectin, AdipoR1, AdipoR2, sphingosine-1-phosphate, sphingolipid metabolism, apoptosis, caspase-8, insulin sensitivity, anti-inflammatory activity, cardiomyocytes, pancreatic beta cells, AMPK, cell survival
- MeSH terms
- Adenylate Kinase, Animals, Ceramides, Enzyme Activation, Gene Expression Regulation, Humans, Insulin, Kinetics, Mice, Obese, Myocardial Infarction, Apoptosis, Leptin, Myocytes, Cardiac, Mice, Adiponectin, Receptors, Adiponectin, Calcium-Calmodulin-Dependent Protein Kinase Kinase, Ceramidases
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
