A Glucagon-Like Peptide-1 Analog Reverses the Molecular Pathology and Cardiac Dysfunction of a Mouse Model of Obesity
Open accessAbstract
Background—: Cardiac consequences of obesity include inflammation, hypertrophy, and compromised energy metabolism. Glucagon-like peptide-1 is an incretin hormone capable of cytoprotective actions that reduces inflammation and endoplasmic reticulum stress in other tissues. Here we examine the cardiac effects of the glucagon-like peptide-1 analog liraglutide in a model of obesity, independent of changes in body weight. Methods and Results—: C57Bl6 mice were placed on a 45% high-fat diet (HFD) or a regular chow diet. Mice on HFD developed 46±2% and 60±2% greater body weight relative to regular chow diet–fed mice at 16 and 32 weeks, respectively (both P <0.0001), manifesting impaired glucose tolerance, insulin resistance, and cardiac ceramide accumulation by 16 weeks. One-week treatment with liraglutide (30 µg/kg twice daily) did not reduce body weight, but reversed insulin resistance, cardiac tumor necrosis factor-α expression, nuclear factor kappa B translocation, obesity-induced perturbations in cardiac endothelial nitric oxide synthase, connexin-43, and markers of hypertrophy and fibrosis, in comparison with placebo-treated HFD controls. Liraglutide improved the cardiac endoplasmic reticulum stress response and also improved cardiac function in animals on HFD by an AMP-activated protein kinase–dependent mechanism. Supporting a direct mechanism of action, liraglutide (100 nmol/L) prevented palmitate-induced lipotoxicity in isolated mouse cardiomyocytes and primary human coronary smooth muscle cells and prevented adhesion of human monocytes to tumor necrosis factor-α–activated human endothelial cells in vitro. Conclusions—: Weight-neutral treatment with a glucagon-like peptide-1 analog activates several cardioprotective pathways, prevents HFD-induced insulin resistance and inflammation, reduces monocyte vascular adhesion, and improves cardiac function in vivo by activating AMP-activated protein kinase. These data support a role for glucagon-like peptide-1 analogs in limiting the cardiovascular risks of obesity.
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?
Antiinflammatory benefits of GLP-1 medicines have been observed in various preclinical models, such as obesity, atherosclerosis, steatohepatitis, and nephritis, even in the absence of direct immune cell targeting.
“antiinflammatory benefits have been observed in various preclinical models, such as obesity, atherosclerosis, steatohepatitis, and nephritis, even in the absence of direct immune cell targeting (27–32).”
From Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits (2025) · cites this paper as [32]
In “Liraglutide Reduced Inflammation in the Hearts of HFD-Fed Mice” (page unavailable), the paper reports reduced cardiac TNF-α and NFκB activation after liraglutide treatment, supporting the obesity example. Its endothelial-cell experiments also show reduced monocyte adhesion, but the paper does not establish that the benefits occurred without direct immune-cell targeting. The other listed disease models are not findings of this study. (LLM, conf=0.83)
Experimental — accuracy not yet measuredTreatment with GLP-1RAs activates several cardioprotective pathways, prevents HFD-induced insulin resistance and inflammation, improves endothelial function, and ameliorates cardiac function in obese mice.
“treatment with GLP-1RAs activates several cardioprotective pathways, prevents HFD-induced insulin resistance and inflammation, improves endothelial function, and ameliorates cardiac function in obese mice.”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [53]
Other vitro studies observed a beneficial effect of GLP-1RAs on ANGII-induced cardiac fibrosis.
“Other vitro studies observed a beneficial effect of GLP-1RAs on ANGII-induced cardiac fibrosis as well.”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [53]
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
2 retracted
Ceylan‐Isik, A. F., Sreejayan, N., & Ren, J. T. (2010) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2010.10.023 · Cited by 101 · see citing works
RetractedAMP-Activated Protein Kinase α1 Protects Against Diet-Induced Insulin Resistance and Obesity
Zhang, W., Zhang, X., Wang, H., Guo, X., Li, H., Wang, Y., Xu, X. Y., Tan, L., Mashek, M. T., Zhang, C., et al. (2012) · Diabetes · doi:10.2337/db11-1373 · Cited by 37 · see citing works
RetractedAdipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518 · see citing works
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143 · see citing works
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844 · see citing works
Inflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754 · see citing works
Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
Hotamisligil, G. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.034 · Cited by 2,802 · see citing works
Protection from obesity-induced insulin resistance in mice lacking TNF-α function
Uysal, K. T., Wiesbrock, S. M., Marino, M. W., & Hotamisligil, G. S. (1997) · Nature · doi:10.1038/39335 · Cited by 2,234 · see citing works
The biology of incretin hormones
Drucker, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.004 · Cited by 2,210 · see citing works
Self-citationHigh‐fat Diets: Modeling the Metabolic Disorders of Human Obesity in Rodents
Buettner, R., Schölmerich, J., & Bollheimer, L. C. (2007) · Obesity · doi:10.1038/oby.2007.608 · Cited by 1,241 · see citing works
Ban, K., Noyan-Ashraf, M. H., Hoefer, J., Bolz, S.-S., Drucker, D. J., & Husain, M. (2008) · Circulation · doi:10.1161/circulationaha.107.739938 · Cited by 1,057 · see citing works
Self-citationAutophagy: assays and artifacts
Barth, S., Glick, D. R., & Macleod, K. F. (2010) · The Journal of Pathology · doi:10.1002/path.2694 · Cited by 794 · see citing works
Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736 · see citing works
McClean, P. L., Parthsarathy, V., Faivre, E., & Hölscher, C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0529-11.2011 · Cited by 698 · see citing works
Noyan-Ashraf, M. H., Momen, M. A., Ban, K., Sadi, A.-M., Zhou, Y.-Q., Riazi, A. M., Baggio, L. L., Henkelman, R. M., Husain, M., & Drucker, D. J. (2009) · Diabetes · doi:10.2337/db08-1193 · Cited by 575 · see citing works
Self-citationKaraskov, E., Scott, C. C., Zhang, L., Teodoro, T., Ravazzola, M., & Volchuk, A. (2006) · Endocrinology · doi:10.1210/en.2005-1494 · Cited by 573 · see citing works
Self-citationArakawa, M., Mita, T., Azuma, K., Ebato, C., Goto, H., Nomiyama, T., Fujitani, Y., Hirose, T., Kawamori, R., & Watada, H. (2010) · Diabetes · doi:10.2337/db09-1694 · Cited by 548 · see citing works
Fazel, S. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27019 · Cited by 512 · see citing works
The Pathogenesis of Myocardial Fibrosis in the Setting of Diabetic Cardiomyopathy
Asbun, J., & Villarreal, F. J. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.09.050 · Cited by 486 · see citing works
Yusta, B., Baggio, L. L., Estall, J. L., Koehler, J. A., Holland, D. P., Li, H., Pipeleers, D., Ling, Z., & Drucker, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.10.001 · Cited by 444 · see citing works
Self-citationGundewar, S., Calvert, J. W., Jha, S. K., Toedt‐Pingel, I., Ji, S. Y., Nunez, D. J., Ramachandran, A., Anaya-Cisneros, M., Tian, R., & Lefer, D. J. (2008) · Circulation Research · doi:10.1161/circresaha.108.190918 · Cited by 422 · see citing works
Novel Metabolic Risk Factors for Incident Heart Failure and Their Relationship With Obesity
Bahrami, H., Bluemke, D. A., Kronmal, R. A., Bertoni, A. G., Lloyd‐Jones, D. M., Shahar, E., Szklo, M., & Lima, J. A. C. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.12.048 · Cited by 365 · see citing works
Metabolic stress–induced activation of FoxO1 triggers diabetic cardiomyopathy in mice
Battiprolu, P. K., Hojayev, B., Jiang, N., Wang, Z. V., Luo, X., Iglewski, M., Shelton, J. M., Gerard, R. D., Rothermel, B. A., Gillette, T. G., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60329 · Cited by 344 · see citing works
TNF- downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents
Valerio, A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28570 · Cited by 327 · see citing works
Kim, E.-K., Miller, I., Aja, S., Landree, L. E., Pinn, M., Mcfadden, J., Kuhajda, F., Moran, T., & Ronnett, G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402165200 · Cited by 302 · see citing works
Lerner, D. L., Yamada, K. A., Schuessler, R. B., et al. (2000) · Circulation · doi:10.1161/01.cir.101.5.547 · Cited by 273 · see citing works
Sharma, S., Mells, J. E., Fu, P. P., Saxena, N. K., & Anania, F. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025269 · Cited by 272 · see citing works
Sauvé, M., Ban, K., Momen, M. A., Zhou, Y., Henkelman, R. M., Husain, M., & Drucker, D. J. (2010) · Diabetes · doi:10.2337/db09-0955 · Cited by 264 · see citing works
Self-citationCoronary Hemodynamics in Endothelial NO Synthase Knockout Mice
Gödecke, A., Decking, U. K. M., Ding, Z., Hirchenhain, J., Bidmon, H. J., Gödecke, S., & Schrader, J. (1998) · Circulation Research · doi:10.1161/01.res.82.2.186 · Cited by 263 · see citing works
Hamid, T., Guo, S. Z., Kingery, J. R., Xiang, X., Dawn, B., & Prabhu, S. D. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq274 · Cited by 253 · see citing works
Ban, K., Kim, K.-H., Cho, C.-K., Sauvé, M., Diamandis, E. P., Backx, P. H., Drucker, D. J., & Husain, M. (2010) · Endocrinology · doi:10.1210/en.2009-1197 · Cited by 225 · see citing works
Self-citationInteraction between free fatty acids and glucose metabolism
Boden, G. H. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200209000-00014 · Cited by 222 · see citing works
Cunha, D. A., Ladrière, L., Ortis, F., Igoillo‐Esteve, M., Gurzov, E. N., Lupi, R., Marchetti, P., Eizirik, D. L., & Cnop, M. (2009) · Diabetes · doi:10.2337/db09-0685 · Cited by 222 · see citing works
Pdx1 ( MODY4 ) regulates pancreatic beta cell susceptibility to ER stress
Sachdeva, M. M., Claiborn, K. C., Khoo, C., Yang, J., Groff, D., Mirmira, R. G., & Stoffers, D. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904849106 · Cited by 221 · see citing works
Mells, J. E., Fu, P. P., Sharma, S., Olson, D., Cheng, L., Handy, J. A., Saxena, N. K., Sorescu, D., & Anania, F. A. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00274.2011 · Cited by 202 · see citing works
Dyntar, D., Eppenberger-Eberhardt, M., Maedler, K., Pruschy, M. N., Eppenberger, H. M., Spinas, G. A., & Donath, M. Y. (2001) · Diabetes · doi:10.2337/diabetes.50.9.2105 · Cited by 194 · see citing works
Free Fatty Acid–Induced Reduction in Glucose-Stimulated Insulin Secretion
Oprescu, A. I., Bikopoulos, G. J., Naassan, A. E., Allister, E. M., Tang, C., Park, E., Uchino, H., Lewis, G. F., Fantus, I. G., Rozakis-Adcock, M., et al. (2007) · Diabetes · doi:10.2337/db07-0075 · Cited by 186 · 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
Wang, Y., Feng, W., Xue, W., Tan, Y., Hein, D. W., Li, X., & Cai, L. (2009) · Diabetes · doi:10.2337/db08-1697 · Cited by 166 · see citing works
Ko, H. J., Zhang, Z., Jung, D. Y., Jun, J. Y., Ma, Z., Jones, K. E., Chan, S. Y., & Kim, J. K. (2009) · Diabetes · doi:10.2337/db08-1361 · Cited by 157 · see citing works
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 141 · see citing works
An Integrative View of Obesity
Wisse, B. E., Kim, F., & Schwartz, M. W. (2007) · Science · doi:10.1126/science.1148032 · Cited by 138 · see citing works
Kondo, M., Shibata, R., Miura, R., Shimano, M., Kondo, K., Li, P., Ohashi, T., Kihara, S., Maeda, N., Walsh, K., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805301200 · Cited by 124 · see citing works
Fernandez-Cobo, M., Gingalewski, C. A., Drujan, D., & Maio, A. D. (1999) · Cytokine · doi:10.1006/cyto.1998.0422 · Cited by 120 · see citing works
Turdi, S., Kandadi, M. R., Zhao, J., Huff, A. F., Du, M., & Ren, J. (2011) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2010.12.007 · Cited by 103 · see citing works
Hoefer, J., Azam, M. A., Kroetsch, J. T., Leong-Poi, H. M., Momen, M. A., Voigtlaender‐Bolz, J., Scherer, E. Q., Meißner, A., Bolz, S., & Husain, M. (2010) · Circulation Research · doi:10.1161/circresaha.110.226464 · Cited by 83 · see citing works
Self-citationHenriksen, E. J. (2010) · Current Diabetes Reviews · doi:10.2174/157339910793360888 · Cited by 75 · see citing works
Remodeling of connexin 43 in the diabetic rat heart
Lin, H., Ogawa, K., Imanaga, I., & Tribulová, N. (2006) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-006-9166-y · Cited by 72 · see citing works
AMP-activated protein kinase confers protection against TNF-α-induced cardiac cell death
Kewalramani, G., Puthanveetil, P., Wang, F., Kim, M. S., Deppe, S., Abrahani, A., Luciani, D. S., Johnson, J. D., & Rodrigues, B. B. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp166 · Cited by 67 · see citing works
Obesity treatment: novel peripheral targets
Field, B. C. T., Chaudhri, O. B., & Bloom, S. R. (2009) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2009.03522.x · Cited by 64 · see citing works
Fatty Acid-Induced Apoptosis in Neonatal Cardiomyocytes: Redox Signaling
Sparagna, G. C., Hickson-Bick, D. L., Buja, L. M., & McMillin, J. B. (2001) · Antioxidants & Redox Signaling · doi:10.1089/152308601750100524 · Cited by 56 · see citing works
Cardiac hypertrophy and sudden death in mice with a genetically clamped renin transgene
Caron, K. M., James, L. R., Kim, H., Knowles, J. W., Uhlir, R., Mao, L., Hagaman, J. R., Cascio, W. E., Rockman, H. A., & Smithies, O. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307333101 · Cited by 50 · see citing works
Electrical remodelling precedes heart failure in an endothelin-1-induced model of cardiomyopathy
Mueller, E. E., Momen, A., Massé, S., et al. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq351 · Cited by 46 · see citing works
Cardiac Fas Receptor‐dependent Apoptotic Pathway in Obese Zucker Rats
Lee, S., Tzang, B., Kuo, W., Lin, Y., Yang, A., Chen, S. H., Tsai, F., Wu, F., Lu, M., & Huang, C. (2007) · Obesity · doi:10.1038/oby.2007.286 · Cited by 42 · see citing works
Kusmic, C., L’Abbate, A., Sambuceti, G., Drummond, G., Barsanti, C., Matteucci, M., Cao, J. J., Piccolomini, F., Cheng, J., & Abraham, N. G. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22486 · Cited by 37 · see citing works
Hui, S., Choi, J., Zaidi, S., et al. (2011) · Circulation Research · doi:10.1161/circresaha.110.239483 · Cited by 18 · see citing works
The Incretin System and Cardiovascular Risk: Effects of Incretin-Targeted Therapies
Mundil, D., Noyan-Ashraf, M. H., & Husain, M. (2010) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-010-0141-5 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Heerspink, H. J. L., Perkins, B. A., Fitchett, D. H., Husain, M., & Cherney, D. Z. I. (2016) · Circulation · doi:10.1161/circulationaha.116.021887 · Cited by 1,376 · see citing works
Self-citationThe Cardiovascular Biology of Glucagon-like Peptide-1
Drucker, D. J. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.009 · Cited by 665 · see citing works
Self-citationGlucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action
Ussher, J. R., & Drucker, D. J. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00849-3 · Cited by 577 · see citing works
Self-citationRakipovski, G., Rolin, B., Nøhr, J., Klewe, I., Frederiksen, K. S., Augustin, R., Hecksher-Sørensen, J., Ingvorsen, C., Polex-Wolf, J., & Knudsen, L. B. (2018) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2018.09.004 · Cited by 509 · see citing works
GLP-1 physiology informs the pharmacotherapy of obesity
Drucker, D. J. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101351 · Cited by 510 · see citing works
Self-citationCardiovascular Actions of Incretin-Based Therapies
Ussher, J. R., & Drucker, D. J. (2014) · Circulation Research · doi:10.1161/circresaha.114.301958 · Cited by 358 · see citing works
Self-citationPleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function
Rowlands, J., Heng, J., Newsholme, P., & Carlessi, R. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00672 · Cited by 302 · see citing works
Wong, C. K., McLean, B. A., Baggio, L. L., Koehler, J. A., Hammoud, R., Rittig, N., Yabut, J. M., Seeley, R. J., Brown, T. J., & Drucker, D. J. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.11.009 · Cited by 304 · see citing works
Self-citationRegulation of Glucose Homeostasis by GLP-1
Nadkarni, P., Chepurny, O. G., & Holz, G. G. (2014) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-800101-1.00002-8 · Cited by 287 · see citing works
Helmstädter, J., Frenis, K., Filippou, K., Grill, A., Dib, M., Kalinovic, S., Pawelke, F., Kus, K., Kröller-Schön, S., Oelze, M., et al. (2020) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atv.0000615456.97862.30 · Cited by 283 · see citing works
Self-citationBeyond the pancreas: contrasting cardiometabolic actions of GIP and GLP1
Hammoud, R., & Drucker, D. J. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00783-3 · Cited by 244 · see citing works
Self-citationThe expanding incretin universe: from basic biology to clinical translation
Drucker, D. J., & Holst, J. J. (2023) · Diabetologia · doi:10.1007/s00125-023-05906-7 · Cited by 243 · see citing works
Self-citationWithaar, C., Meems, L. M. G., Markousis-Mavrogenis, G., Boogerd, C. J., Silljé, H. H. W., Schouten, E. M., Dokter, M. M., Voors, A. A., Westenbrink, B. D., Lam, C. S. P., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa256 · Cited by 223 · see citing works
Salameh, T. S., Rhea, E. M., Talbot, K., & Banks, W. A. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114187 · Cited by 188 · see citing works
Tashiro, Y., Sato, K., Watanabe, T., Nohtomi, K., Terasaki, M., Nagashima, M., & Hirano, T. (2014) · Peptides · doi:10.1016/j.peptides.2013.12.015 · Cited by 149 · see citing works
Lambadiari, V., Pavlidis, G., Kousathana, F., Varoudi, M., Vlastos, D., Maratou, E., Georgiou, D., Andreadou, I., Parissis, J., Triantafyllidi, H., et al. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0646-z · Cited by 146 · see citing works
Vinué, Á., Navarro, J., Herrero-Cervera, A., García-Cubas, M., Andrés-Blasco, I., Martínez-Hervás, S., Real, J. T., Ascaso, J. F., & González-Navarro, H. (2017) · Diabetologia · doi:10.1007/s00125-017-4330-3 · Cited by 137 · see citing works
Younce, C. W., Burmeister, M. A., & Ayala, J. E. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00248.2012 · Cited by 134 · see citing works
Wong, C. K., Yusta, B., Koehler, J. A., Baggio, L. L., McLean, B. A., Matthews, D., Seeley, R. J., & Drucker, D. J. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.08.003 · Cited by 138 · see citing works
Self-citationBizino, M. B., Jazet, I. M., de Heer, P., van Eyk, H. J., Dekkers, I. A., Rensen, P. C. N., Paiman, E. H. M., Lamb, H. J., & Smit, J. W. (2020) · Diabetologia · doi:10.1007/s00125-019-05021-6 · Cited by 123 · see citing works
Zhu, Y., Gao, Y., Tao, C., Shao, M., Zhao, S., Huang, W., Yao, T., Johnson, J. A., Liu, T., Cypess, A. M., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.005 · Cited by 100 · see citing works
Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits
Wong, C. K., & Drucker, D. J. (2025) · Journal of Clinical Investigation · doi:10.1172/jci194751 · Cited by 112 · see citing works
“…GLP-1R expression in peripheral tissues is generally low and restricted to rare cell types (26), antiinflammatory benefits have been observed in various preclinical models, such as obesity, atherosclerosis, steatohepatitis, and nephritis, even in the absence of direct immune cell targeting (27–32).”
Self-citationHelmstädter, J., Keppeler, K., Küster, L., Münzel, T., Daiber, A., & Steven, S. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15462 · Cited by 99 · see citing works
Shi, L., Ji, Y., Jiang, X., Zhou, L., Xu, Y., Li, Y., Jiang, W., Meng, P., & Liu, X. (2015) · Cardiovascular Diabetology · doi:10.1186/s12933-015-0177-4 · Cited by 91 · see citing works
McLean, B. A., Wong, C. K., Kabir, M. G., & Drucker, D. J. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101641 · Cited by 82 · see citing works
“T a subset of genes important for the control of inflammation in the mouse atria, consistent with the known anti-inflammatory actions of GLP-1RA in multiple tissues [57], including the normal and injured heart [14,57,58].”
BackgroundSelf-citationThe cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF
Withaar, C., Meems, L. M. G., Nollet, E. E., Schouten, E. M., Schroeder, M. A., Knudsen, L. B., Niss, K., Madsen, C. T., Hoegl, A., Mazzoni, G., et al. (2023) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2023.05.012 · Cited by 74 · see citing works
AMPK is associated with the beneficial effects of antidiabetic agents on cardiovascular diseases
Lu, Q., Li, X., Liu, J., Sun, X., Rousselle, T., Ren, D., Tong, N., & Li, J. (2019) · Bioscience Reports · doi:10.1042/bsr20181995 · Cited by 69 · see citing works
Cardiometabolic effects of a new class of antidiabetic agents
Desouza, C. V., Gupta, N., & Patel, A. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.02.016 · Cited by 54 · see citing works
GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms
Mullur, N., Morissette, A., Morrow, N. M., & Mulvihill, E. E. (2024) · Journal of Endocrinology · doi:10.1530/joe-24-0046 · Cited by 51 · see citing works
Tang, S.-T., Zhang, Q., Tang, H.-Q., Wang, C.-J., Su, H., Zhou, Q., Wei, W., Zhu, H.-Q., & Wang, Y. (2016) · Endocrine · doi:10.1007/s12020-015-0852-y · Cited by 46 · see citing works
Direct cardiovascular effects of glucagon like peptide-1
Sheikh, A. (2013) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-5-47 · Cited by 45 · see citing works
Ji, W., Chen, X., Lv, J., Wang, M., Ren, S., Yuan, B., Wang, B., & Chen, L. (2014) · International Journal of Endocrinology · doi:10.1155/2014/312452 · Cited by 36 · see citing works
Novel GLP-1-based Medications for Type 2 Diabetes and Obesity
Son, J. W., le Roux, C. W., Blüher, M., Nauck, M. A., & Lim, S. (2026) · Endocrine Reviews · doi:10.1210/endrev/bnaf036 · Cited by 33 · see citing works
Chen, P., Yang, F., Wang, W., Li, X., Liu, D., Zhang, Y., Yin, G., Lv, F., Guo, Z., Mehta, J. L., et al. (2021) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248420942007 · Cited by 31 · see citing works
Jensen, S. B. K., Lundgren, J. R., Janus, C., Juhl, C. R., Olsen, L. M., Rosenkilde, M., Holst, J. J., Stallknecht, B. M., Madsbad, S., & Torekov, S. S. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-031431 · Cited by 20 · see citing works
- Authors
- Noyan-Ashraf, M. H., Shikatani, E. A., Schuiki, I., Mukovozov, I., Wu, J., Li, R.-K., Volchuk, A., Robinson, L. A., Billia, F., Drucker, D. J., & Husain, M.
- Affiliations
- University of Toronto (CA)
- ORCID
- Venue
- Circulation
- Published
- 2013-01
- Volume
- 127
- Issue
- 1
- Pages
- 74-85
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2065623326
- Cited by
- 259
- References
- 57
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 23 · 2023: 15 · 2022: 16 · 2021: 15 · 2020: 21 · 2019: 16 · 2018: 15 · 2017: 15 · 2016: 21 · 2015: 29 · 2014: 31 · 2013: 13
- FWCI
- 14.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Novo Nordisk
- Canadian Institutes of Health Research (114922_1)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- glucagon-like peptide-1 analogues, liraglutide, obesity, cardiac dysfunction, high-fat diet, insulin resistance, endoplasmic reticulum stress, AMPK, ceramide accumulation, cardiac inflammation, TNF-α, NF-κB, endothelial nitric oxide synthase, connexin 43, cardiac hypertrophy, myocardial fibrosis, lipotoxicity, monocyte adhesion
- MeSH terms
- Liraglutide, Animals, Blood Glucose, Cardiotonic Agents, Cell Line, Coronary Vessels, Disease Models, Animal, Heart Diseases, Humans, Hypercholesterolemia, Insulin Resistance, Mice, Inbred C57BL, Monocytes, Muscle, Smooth, Vascular, Obesity, Risk Factors, Tumor Necrosis Factor-alpha, Signal Transduction, Gene Expression, Connexin 43, Myocytes, Cardiac, Endothelial Cells, Mice, Glucagon-Like Peptide 1, Nitric Oxide Synthase Type III, Endoplasmic Reticulum Stress
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
