Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis
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We previously suggested that, in obese animals and humans, white adipose tissue inflammation results from the death of hypertrophic adipocytes; these are then cleared by macrophages, giving rise to distinctive structures we denominated crown-like structures. Here we present evidence that subcutaneous and visceral hypertrophic adipocytes of leptin-deficient (ob/ob and db/db) obese mice exhibit ultrastructural abnormalities (including calcium accumulation and cholesterol crystals), many of which are more common in hyperglycemic db/db versus normoglycemic ob/ob mice and in visceral versus subcutaneous depots. Degenerating adipocytes whose intracellular content disperses in the extracellular space were also noted in obese mice; in addition, increased anti-reactive oxygen species enzyme expression in obese fat pads, documented by RT-PCR and immunohistochemistry, suggests that ultrastructural changes are accompanied by oxidative stress. RT-PCR showed NLRP3 inflammasome activation in the fat pads of both leptin-deficient and high-fat diet obese mice, in which formation of active caspase-1 was documented by immunohistochemistry in the cytoplasm of several hypertrophic adipocytes. Notably, caspase-1 was not detected in FAT-ATTAC transgenic mice, where adipocytes die of apoptosis. Thus, white adipocyte overexpansion induces a stress state that ultimately leads to death. NLRP3-dependent caspase-1 activation in hypertrophic adipocytes likely induces obese adipocyte death by pyroptosis, a proinflammatory programmed cell death.
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The unique enrichment of genes involved in calcium transport and ossification in hypertrophic Ad4 adipocytes may account for the frequent occurrence of calcium deposits observed in obese adipocytes.
“Also, the unique enrichment of genes involved in calcium transport and ossification in hypertrophic Ad4 adipocytes may account for the frequent occurrence of calcium deposits observed in obese adipocytes (Giordano et al., 2013).”
From Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity (2025) · cites this paper as Giordano et al., 2013
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Cites
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041 · see citing works
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760 · see citing works
Metabolic Endotoxemia Initiates Obesity and Insulin Resistance
Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A. M., Fava, F., Tuohy, K. M., Chabo, C., et al. (2007) · Diabetes · doi:10.2337/db06-1491 · Cited by 6,638 · see citing works
Schroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475 · see citing works
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026 · see citing works
Pyroptosis: host cell death and inflammation
Bergsbaken, T., Fink, S. L., & Cookson, B. T. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2070 · Cited by 3,185 · see citing works
Cryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080 · see citing works
Macrophages, inflammation, and insulin resistance
Olefsky, J. M., & Glass, C. K. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135846 · Cited by 2,733 · see citing works
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Zhou, R., Tardivel, A., Thorens, B., Choi, I., & Tschopp, J. (2010) · Nature Immunology · doi:10.1038/ni.1831 · Cited by 2,708 · see citing works
The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Vandanmagsar, B., Youm, Y.-H., Ravussin, A., Galgani, J. E., Stadler, K., Mynatt, R. L., Ravussin, E., Stephens, J. M., & Dixit, V. D. (2011) · Nature Medicine · doi:10.1038/nm.2279 · Cited by 2,655 · see citing works
Pathophysiology of human visceral obesity: an update
Tchernof, A., & Després, J.-P. (2013) · Physiological Reviews · doi:10.1152/physrev.00033.2011 · Cited by 2,583 · see citing works
Cinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A. S., & Obin, M. S. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500294-jlr200 · Cited by 2,529 · see citing works
Self-citationInterleukin-1-receptor antagonist in type 2 diabetes mellitus
Larsen, C. M., Faulenbach, M., Vaag, A., Vølund, A., Ehses, J. A., Seifert, B., Mandrup-Poulsen, T., & Donath, M. Y. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065213 · Cited by 1,798 · see citing works
The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP
Lee, G., Subramanian, N., Kim, A. I., Aksentijevich, I. A., Goldbach‐Mansky, R. T., Sacks, D. B., Germain, R. N., Kastner, D. L., & Chae, J. J. (2012) · Nature · doi:10.1038/nature11588 · Cited by 1,077 · see citing works
Rajamäki, K., Lappalainen, J., Öörni, K., Välimäki, E., Matikainen, S., Kovanen, P. T., & Eklund, K. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011765 · Cited by 1,039 · see citing works
Adipocyte Death, Adipose Tissue Remodeling, and Obesity Complications
Strissel, K. J., Stancheva, Z., Miyoshi, H., Perfield, J. W., DeFuria, J., Jick, Z., Greenberg, A. S., & Obin, M. S. (2007) · Diabetes · doi:10.2337/db07-0767 · Cited by 1,007 · see citing works
Hypoxia-Inducible Factor 1α Induces Fibrosis and Insulin Resistance in White Adipose Tissue
Halberg, N., Khan, T., Trujillo, M. E., Wernstedt-Asterholm, I., Attie, A. D., Sherwani, S., Wang, Z. V., Landskroner-Eiger, S., Dineen, S., Magalang, U. J., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00192-09 · Cited by 896 · see citing works
Self-citationHypoxia and Adipose Tissue Function and Dysfunction in Obesity
Trayhurn, P. (2013) · Physiological Reviews · doi:10.1152/physrev.00017.2012 · Cited by 884 · see citing works
Lin, S., Kisseleva, T., Brenner, D. A., & Duffield, J. S. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080433 · Cited by 834 · see citing works
Inflammatory caspases and inflammasomes: master switches of inflammation
Martinon, F., & Tschopp, J. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402038 · Cited by 821 · see citing works
Ultrastructural Pathology of the Cell and Matrix
(1988) · Elsevier eBooks · doi:10.1016/c2013-0-06247-0 · Cited by 785 · see citing works
Inflammasome is a central player in the induction of obesity and insulin resistance
Stienstra, R., van Diepen, J. A., Tack, C. J., Zaki, M. H., van de Veerdonk, F. L., Perera, D., Neale, G. A., Hooiveld, G. J., Hijmans, A., Vroegrijk, I., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100255108 · Cited by 727 · see citing works
Murano, I., Barbatelli, G., Parisani, V., Latini, C., Muzzonigro, G., Castellucci, M., & Cinti, S. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800019-jlr200 · Cited by 726 · see citing works
Self-citationJager, J., Grémeaux, T., Cormont, M., MARCHAND‐BRUSTEL, Y. L., & Tanti, J. (2006) · Endocrinology · doi:10.1210/en.2006-0692 · Cited by 697 · see citing works
Stienstra, R., Joosten, L. A. B., Koenen, T. B., van Tits, B. L. J. H., van Diepen, J. A., van den Berg, S. A. A., Rensen, P. C. N., Voshol, P. J., Fantuzzi, G., Hijmans, A., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.011 · Cited by 681 · see citing works
The Origins and Drivers of Insulin Resistance
Johnson, A. M. F., & Olefsky, J. M. (2013) · Cell · doi:10.1016/j.cell.2013.01.041 · Cited by 639 · see citing works
What causes the insulin resistance underlying obesity?
Hardy, O. T., Czech, M. P., & Corvera, S. (2012) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0b013e3283514e13 · Cited by 563 · see citing works
The role of mitochondria in the pathogenesis of type 2 diabetes
Patti, M.-E., & Corvera, S. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0027 · Cited by 551 · see citing works
Endoplasmic Reticulum Stress and Inflammation in Obesity and Diabetes
Hummasti, S., & Hotamışlıgil, G. S. (2010) · Circulation Research · doi:10.1161/circresaha.110.225698 · Cited by 436 · see citing works
Londos, C., Brasaemle, D., Schultz, C. J., Segrest, J. P., & Kimmel, A. R. (1999) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.1998.0275 · Cited by 435 · see citing works
Role of IL-1β in type 2 diabetes
Dinarello, C. A., Donath, M. Y., & Mandrup-Poulsen, T. R. (2010) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0b013e32833bf6dc · Cited by 330 · see citing works
Pajvani, 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-citationSouza, S. C., de Vargas, L. M., Yamamoto, M. T., Lien, P., Franciosa, M. D., Moss, L. G., & Greenberg, A. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.38.24665 · Cited by 283 · see citing works
Cellularity of adipose depots in six strains of genetically obese mice
Johnson, P. R., & Hirsch, J. (1972) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39428-1 · Cited by 278 · see citing works
Visceral fat and metabolic inflammation: the portal theory revisited
Item, F., & Konrad, D. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01035.x · Cited by 273 · see citing works
Ultrastructural Pathology of the Cell and Matrix
de Harven, É. (1988) · Elsevier eBooks · doi:10.1016/c2013-0-06246-9 · Cited by 253 · see citing works
The Adipose Tissue Phenotype of Hormone‐Sensitive Lipase Deficiency in Mice
Wang, S. P., Laurin, N., Himms‐Hagen, J., Rudnicki, M. A., Levy, E. H., Robert, M., Pan, L., Oligny, L. L., & Mitchell, G. A. (2001) · Obesity Research · doi:10.1038/oby.2001.15 · Cited by 236 · see citing works
Adipose tissue and cholesterol metabolism.
Krause, B. R., & Hartman, A. D. (1984) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37830-5 · Cited by 212 · see citing works
Architecture and the extracellular matrix: the still unappreciated components of the adipose tissue
Divoux, A., & Clément, K. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2010.00811.x · Cited by 206 · see citing works
Oxidant mechanisms in childhood obesity: the link between inflammation and oxidative stress
Codoñer‐Franch, P., Valls‐Bellés, V., Arilla-Codoñer, Á., & Alonso‐Iglesias, E. (2011) · Translational research · doi:10.1016/j.trsl.2011.08.004 · Cited by 189 · see citing works
The adipose organ: white‐brown adipocyte plasticity and metabolic inflammation
Smorlesi, A., Frontini, A., Giordano, A., & Cinti, S. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01039.x · Cited by 179 · see citing works
Self-citationHyperglycemia Activates Caspase-1 and TXNIP-Mediated IL-1β Transcription in Human Adipose Tissue
Koenen, T. B., Stienstra, R., van Tits, L. J., Graaf, J. D., Stalenhoef, A. F. H., Joosten, L. A. B., Tack, C. J., & Netea, M. G. (2011) · Diabetes · doi:10.2337/db10-0266 · Cited by 171 · see citing works
Treatment with an Interleukin 1 beta antibody improves glycemic control in diet-induced obesity
Osborn, O., Brownell, S. E., Sanchez-Alavez, M., Salomon, D., Gram, H., & Bartfai, T. (2008) · Cytokine · doi:10.1016/j.cyto.2008.07.004 · Cited by 160 · see citing works
Rodríguez‐Calvo, R., Serrano, L., Coll, T., Moullan, N., Sánchez, R. M., Merlos, M., Palomer, X., Laguna, J. C., Michalik, L., Wahli, W., et al. (2008) · Diabetes · doi:10.2337/db08-0176 · Cited by 121 · see citing works
Rungby, J., Kassem, M. S., Eriksen, E. F., & Danscher, G. (1993) · The Histochemical Journal · doi:10.1007/bf00157809 · Cited by 92 · see citing works
Non-Neoplastic Kidney Diseases
D’Agati, V. D., Jennette, J. C., & Silva, F. G. (2005) · American Registry of PathologyWashington, DC eBooks · doi:10.55418/1881041964 · Cited by 79 · see citing works
Time course of histomorphological changes in adipose tissue upon acute lipoatrophy
Murano, I., Rutkowski, J. M., Wang, Q. A., Cho, Y.-R., Scherer, P. E., & Cinti, S. (2012) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2012.03.005 · Cited by 53 · see citing works
Self-citationTrujillo, M. E., Pajvani, U. B., & Scherer, P. E. (2005) · Cell Cycle · doi:10.4161/cc.4.9.2030 · Cited by 30 · see citing works
Self-citationRiva, A., Congiu, T., & Faa, G. (1993) · Microscopy Research and Technique · doi:10.1002/jemt.1070260610 · Cited by 16 · see citing works
Further data on intracellular structure of human salivary glands. A SEM study
Riva, A., Riva, F. T., Congiu, T., & Loffredo, F. (1996) · European Journal of Morphology · doi:10.1076/ejom.34.3.209.13036 · Cited by 7 · see citing works
Tensions Rise and Blood Flows Over Dysfunctional Fat
Corvera, S., & Czech, M. (2011) · Circulation · doi:10.1161/circulationaha.111.037804 · Cited by 6 · see citing works
Non-Neoplastic Kidney Diseases
Drachenberg, C. B. (2006) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2006.02.188 · Cited by 6 · see citing works
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Inflammaging: a new immune–metabolic viewpoint for age-related diseases
Franceschi, C., Garagnani, P., Parini, P., Giuliani, C., & Santoro, A. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0059-4 · Cited by 3,586 · see citing works
Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms
Petrie, J. R., Guzik, T. J., & Touyz, R. M. (2018) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.12.005 · Cited by 1,787 · see citing works
Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders
Choe, S. S., Huh, J. Y., Hwang, I. J., Kim, J. I., & Kim, J. B. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00030 · Cited by 1,206 · see citing works
Cohen, P., Levy, J. D., Zhang, Y., Frontini, A., Kolodin, D., Svensson, K. J., Lo, J. C., Zeng, X., Ye, L., Khandekar, M. J., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.021 · Cited by 878 · see citing works
Self-citationMacrophage-Mediated Inflammation in Normal and Diabetic Wound Healing
Boniakowski, A. E., Kimball, A., Jacobs, B. N., Kunkel, S. L., & Gallagher, K. A. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700223 · Cited by 546 · see citing works
The obese adipose tissue microenvironment in cancer development and progression
Quail, D. F., & Dannenberg, A. J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0126-x · Cited by 542 · see citing works
Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics
Morigny, P., Boucher, J., Arner, P., & Langin, D. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00471-8 · Cited by 527 · see citing works
Adipose tissue as an immunological organ
Grant, R. W., & Dixit, V. D. (2015) · Obesity · doi:10.1002/oby.21003 · Cited by 453 · see citing works
Regulation of adipocyte lipolysis
Frühbeck, G., Méndez-Giménez, L., Fernández-Formoso, J., Fernández, S., & Rodríguez, A. (2014) · Nutrition research reviews · doi:10.1017/s095442241400002x · Cited by 380 · see citing works
Adipose tissue macrophages: going off track during obesity
Boutens, L., & Stienstra, R. (2016) · Diabetologia · doi:10.1007/s00125-016-3904-9 · Cited by 430 · see citing works
Liu, Z., Gan, L., Xu, Y., Luo, D., Ren, Q., Wu, S., & Sun, C. (2017) · Journal of Pineal Research · doi:10.1111/jpi.12414 · Cited by 363 · see citing works
Qiu, Z., Lei, S., Zhao, B., Wu, Y., Su, W., Liu, M., Meng, Q., Zhou, B., Leng, Y., & Xia, Z. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/9743280 · Cited by 351 · see citing works
Insulin resistance in obesity: an overview of fundamental alterations
Barazzoni, R., Cappellari, G. G., Ragni, M., & Nisoli, E. (2018) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-018-0481-6 · Cited by 375 · see citing works
Self-citationCalcium Homeostasis and Organelle Function in the Pathogenesis of Obesity and Diabetes
Arruda, A. P., & Hotamışlıgil, G. S. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.010 · Cited by 338 · see citing works
Pyroptosis, metabolism, and tumor immune microenvironment
Du, T., Gao, J., Li, P., Wang, Y., Qi, Q., Liu, X., Li, J., Wang, C., & Du, L. (2021) · Clinical and Translational Medicine · doi:10.1002/ctm2.492 · Cited by 325 · see citing works
Tarocco, A., Caroccia, N., Morciano, G., Wieckowski, M. R., Ancora, G., Garani, G., & Pinton, P. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1556-7 · Cited by 307 · see citing works
Hersoug, L., Møller, P., & Loft, S. H. (2015) · Obesity Reviews · doi:10.1111/obr.12370 · Cited by 294 · see citing works
Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation
Kotzbeck, P., Giordano, A., Mondini, E., Murano, I., Severi, I., Venema, W., Cecchini, M. P., Kershaw, E. E., Barbatelli, G., Haemmerle, G., et al. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m079665 · Cited by 294 · see citing works
Self-citationThe Pathogenesis of Obesity-Associated Adipose Tissue Inflammation
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_9 · Cited by 291 · see citing works
Macrophage Related Chronic Inflammation in Non-Healing Wounds
Li, M., Hou, Q., Zhong, L., Zhao, Y., & Fu, X. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.681710 · Cited by 299 · see citing works
Role of Pyroptosis in Cardiovascular Diseases and its Therapeutic Implications
Zeng, C., Wang, R., & Tan, H. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.33568 · Cited by 285 · see citing works
Rodrı́guez, A., Ezquerro, S., Méndez-Giménez, L., Becerril, S., & Frühbeck, G. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00297.2015 · Cited by 281 · see citing works
Giordano, A., Smorlesi, A., Frontini, A., Barbatelli, G., & Cinti, S. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-0945 · Cited by 279 · see citing works
Self-citationDeciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis
Marcelin, G., Silveira, A. L. M., Martins, L. B., Ferreira, A. V. M., & Clément, K. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129192 · Cited by 274 · see citing works
Hersoug, L., Möller, P., & Loft, S. H. (2018) · Nutrition Research Reviews · doi:10.1017/s0954422417000269 · Cited by 246 · see citing works
Convertible visceral fat as a therapeutic target to curb obesity
Giordano, A., Frontini, A., & Cinti, S. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.31 · Cited by 232 · see citing works
Self-citationMelatonin as an anti-inflammatory agent modulating inflammasome activation
Favero, G., Franceschetti, L., Bonomini, F., Rodella, L. F., & Rezzani, R. (2017) · International Journal of Endocrinology · doi:10.1155/2017/1835195 · Cited by 233 · see citing works
Inflammaging: Implications in Sarcopenia
Antuña, E., Cachán-Vega, C., Bermejo-Millo, J. C., Potes, Y., Caballero, B., Vega‐Naredo, I., Coto‐Montes, A. M., & García-González, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315039 · Cited by 223 · see citing works
Aging, obesity, sarcopenia and the effect of diet and exercise intervention
Colleluori, G., & Villareal, D. T. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111561 · Cited by 207 · see citing works
The initiation of metabolic inflammation in childhood obesity
Singer, K., & Lumeng, C. N. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88882 · Cited by 194 · see citing works
The complex immunological and inflammatory network of adipose tissue in obesity
Apostolopoulos, V., de Courten, M., Stojanovska, L., Blatch, G. L., Tangalakis, K., & de Courten, B. V. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500272 · Cited by 186 · see citing works
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Farrell, G. C., Haczeyni, F., & Chitturi, S. (2018) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-10-8684-7_3 · Cited by 178 · see citing works
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Cummins, T. D., Holden, C. R., Sansbury, B. E., Gibb, A., Shah, J., Zafar, N., Tang, Y., Hellmann, J. L., Rai, S. N., Spite, M. R., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00271.2013 · Cited by 169 · see citing works
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Self-citationFree radicals and male reproduction.
Agarwal, A. K., & Allamaneni, S. S. R. (2011) · PubMed · Cited by 154 · see citing works
Adipose Tissue Fibrosis: Mechanisms, Models, and Importance
DeBari, M. K., & Abbott, R. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176030 · Cited by 141 · see citing works
NLRP3 inflammasome: a key player in the pathogenesis of life-style disorders
Ramachandran, R., Manan, A., Kim, J., & Choi, S. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01261-8 · Cited by 142 · see citing works
Macrophage activation in human diseases
Schultze, J. L., Schmieder, A., & Goerdt, S. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.07.003 · Cited by 130 · see citing works
Haka, A. S., Barbosa-Lorenzi, V. C., Lee, H. J., Falcone, D. J., Hudis, C. A., Dannenberg, A. J., & Maxfield, F. R. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m064089 · Cited by 130 · see citing works
Omental adipose tissue fibrosis and insulin resistance in severe obesity
Guglielmi, V., Cardellini, M., Cinti, F., Corgosinho, F. C., Cardolini, I., D’Adamo, M., Zingaretti, M. C., Bellia, A., Lauro, D., Gentileschi, P., et al. (2015) · Nutrition and Diabetes · doi:10.1038/nutd.2015.22 · Cited by 122 · see citing works
Self-citationInflammasomes and Metabolic Disorders: Old Genes in Modern Diseases
Robbins, G. R., Wen, H., & Ting, J. P. ‐. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.029 · Cited by 114 · see citing works
Macrophages and the Regulation of Adipose Tissue Remodeling
Martinez-Santibañez, G., & Nien-Kai Lumeng, C. (2014) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071812-161113 · Cited by 111 · see citing works
Zhou, L., Park, S., Xu, L. M., Xia, X., Ye, J., Su, L., Jeong, K.-H., Hur, J. H., Oh, H., Tamori, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms6949 · Cited by 107 · see citing works
Self-citationCidea improves the metabolic profile through expansion of adipose tissue
Abreu-Vieira, G., Fischer, A. W., Mattsson, C. L., de Jong, J. M. A., Shabalina, I. G., Rydén, M., Laurencikiene, J., Arner, P., Cannon, B., Nedergaard, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms8433 · Cited by 104 · see citing works
Ke, R., Wang, Y., Hong, S., & Xiao, L. (2020) · Experimental Cell Research · doi:10.1016/j.yexcr.2020.112293 · Cited by 104 · see citing works
Are Obesity-Related Insulin Resistance and Type 2 Diabetes Autoimmune Diseases?
Tsai, S. J., Clemente‐Casares, X., Revelo, X. S., Winer, S., & Winer, D. A. (2015) · Diabetes · doi:10.2337/db14-1488 · Cited by 103 · see citing works
Lipids, inflammasomes, metabolism, and disease
Anand, P. (2020) · Immunological Reviews · doi:10.1111/imr.12891 · Cited by 104 · see citing works
Cimini, F. A., Barchetta, I., Carotti, S., Bertoccini, L., Baroni, M. G., Vespasiani-Gentilucci, U., Cavallo, M.-G., & Morini, S. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i19.3407 · Cited by 101 · see citing works
Adipose tissue inflammation in glucose metabolism
Kammoun, H. L., Kraakman, M. J., & Febbraio, M. A. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9274-4 · Cited by 99 · see citing works
Karastergiou, K., & Fried, S. K. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-70178-3_3 · Cited by 101 · see citing works
Herrero‐Beaumont, G., Pérez-Baos, S., Sánchez‐Pernaute, O., Roman‐Blas, J. A., Lamuedra, A., & Largo, R. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.02.030 · Cited by 98 · see citing works
Ketogenic diet as a potential intervention for lipedema
Keith, L., Seo, C. A., Rowsemitt, C. N., Pfeffer, M., Wahi, M. M., Staggs, M., Dudek, J. E., Gower, B. A., & Carmody, M. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.110435 · Cited by 97 · see citing works
Obesity phenotypes: depot-differences in adipose tissue and their clinical implications
Guglielmi, V., & Sbraccia, P. (2017) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-017-0467-9 · Cited by 97 · see citing works
Tinkov, A. A., Bjørklund, G., Skalny, A. V., Holmgren, A., Геннадиевна, С. М., Chirumbolo, S., & Aaseth, J. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2745-8 · Cited by 94 · see citing works
Camastra, S., Vitali, A., Anselmino, M., Gastaldelli, A., Bellini, R., Berta, R., Severi, I., Baldi, S., Astiarraga, B., Barbatelli, G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-08444-6 · Cited by 93 · see citing works
Self-citationMorphological and Inflammatory Changes in Visceral Adipose Tissue During Obesity
Revelo, X. S., Luck, H., Winer, S., & Winer, D. A. (2013) · Endocrine Pathology · doi:10.1007/s12022-013-9288-1 · Cited by 98 · see citing works
The NLRP3 inflammasome regulates adipose tissue metabolism
Barra, N. G., Henriksbo, B. D., Anhê, F. F., & Schertzer, J. D. (2020) · Biochemical Journal · doi:10.1042/bcj20190472 · Cited by 92 · see citing works
Melatonin reduces obesity and restores adipokine patterns and metabolism in obese ( ob/ob ) mice
Favero, G., Stacchiotti, A., Castrezzati, S., Bonomini, F., Albanese, M., Rezzani, R., & Rodella, L. F. (2015) · Nutrition Research · doi:10.1016/j.nutres.2015.07.001 · Cited by 91 · see citing works
NLRP3 Inflammasome: The Stormy Link Between Obesity and COVID-19
López-Reyes, A. G., Martínez-Armenta, C., Espinosa-Velázquez, R., Vázquez-Cárdenas, P., Cruz‐Ramos, M., Palacios‐González, B., Gómez-Quiroz, L. E., & Martínez‐Nava, G. A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.570251 · Cited by 90 · see citing works
Kar, S., Shahshahan, H. R., Hackfort, B. T., Yadav, S. K., Yadav, R., Kambis, T. N., Lefer, D. J., & Mishra, P. K. (2019) · Antioxidants · doi:10.3390/antiox8120638 · Cited by 85 · see citing works
Yin, Z., Deng, T., Peterson, L. E., Yu, R., Lin, J., Hamilton, D. J., Reardon, P. R., Sherman, V., Winnier, G. E., Zhan, M., et al. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.06.018 · Cited by 85 · see citing works
Anti-Inflammatory Effects of Melatonin in Obesity and Hypertension
Prado, N. J., Ferder, L., Manucha, W. A., & Diez, E. R. (2018) · Current Hypertension Reports · doi:10.1007/s11906-018-0842-6 · Cited by 85 · see citing works
Mammary gland adipocytes in lactation cycle, obesity and breast cancer
Colleluori, G., Perugini, J., Barbatelli, G., & Cinti, S. (2021) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09633-5 · Cited by 82 · see citing works
Self-citationDai, X., Li, X., Zhu, S., Li, M., Zhao, Y. P., Talukder, M., Li, Y., & Li, J. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c06534 · Cited by 81 · see citing works
Caspases in metabolic disease and their therapeutic potential
Wilson, C. H., & Kumar, S. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0111-x · Cited by 80 · see citing works
Reappraisal of Adipose Tissue Inflammation in Obesity
Engin, A. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-63657-8_10 · Cited by 82 · see citing works
Obesity: a perfect storm for carcinogenesis
Harris, B. H. L., Macaulay, V. M., Harris, D. A., Klenerman, P., Karpe, F., Lord, S., Harris, A. L., & Buffa, F. M. (2022) · Cancer and Metastasis Reviews · doi:10.1007/s10555-022-10046-2 · Cited by 80 · see citing works
Matar, D. B., Zhra, M., Nassar, W. K., Altemyatt, H., Naureen, A., Abotouk, N., Elahi, M. A., & Aljada, A. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1592683 · Cited by 80 · see citing works
Fat Cell and Fatty Acid Turnover in Obesity
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_6 · Cited by 73 · see citing works
Lipodystrophy: A paradigm for understanding the consequences of "overloading" adipose tissue
Lim, K., Haider, A., Adams, C., Sleigh, A., & Savage, D. B. (2020) · Physiological Reviews · doi:10.1152/physrev.00032.2020 · Cited by 68 · see citing works
Fat mass- and obesity-associated gene Fto affects the dietary response in mouse white adipose tissue
Ronkainen, J., Huusko, T. J., Soininen, R., Mondini, E., Cinti, F., Mäkelä, K. A., Kovalainen, M., Herzig, K., Järvelin, M., Sebert, S. P., et al. (2015) · Scientific Reports · doi:10.1038/srep09233 · Cited by 67 · see citing works
Self-citationAdipose tissue fibrosis: the unwanted houseguest invited by obesity
Gliniak, C. M., Pedersen, L., & Scherer, P. E. (2023) · Journal of Endocrinology · doi:10.1530/joe-23-0180 · Cited by 69 · see citing works
Self-citationThe Infrapatellar Adipose Body: A Histotopographic Study
Macchi, V., Porzionato, A., Sarasin, G., Petrelli, L., Guidolin, D., Rossato, M., Fontanella, C. G., NATALI, A. N., & De, R. (2016) · Cells Tissues Organs · doi:10.1159/000442876 · Cited by 66 · see citing works
Perforin Is a Novel Immune Regulator of Obesity-Related Insulin Resistance
Revelo, X. S., Tsai, S. J., Lei, H., Luck, H., Ghazarian, M., Tsui, H., Shi, S. Y., Schroer, S. A., Luk, C. T., Lin, G. H. Y., et al. (2014) · Diabetes · doi:10.2337/db13-1524 · Cited by 65 · see citing works
Faria, S. S., Corrêa, L. H., Cardoso, G. S. H. R., de Sant’Ana, L. P., Almeida, R. D. N., & Magalhães, K. G. (2020) · Journal of Breast Cancer · doi:10.4048/jbc.2020.23.e35 · Cited by 65 · see citing works
Dietary cholesterol effects on adipose tissue inflammation
Chung, S., & Parks, J. S. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000260 · Cited by 63 · see citing works
Castillo, Í. M. P., Argilés, J. M. A., Rueda, R., Ramírez, M., & Pedrosa, J. M. L. (2025) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-025-09954-9 · Cited by 66 · see citing works
Rudnicki, M., Abdifarkosh, G., Nwadozi, E., Ramos, S. V., Makki, A., Sepa-Kishi, D. M., Ceddia, R. B., Perry, C. G. R., Roudier, E. A., & Haas, T. L. (2018) · eLife · doi:10.7554/elife.39780 · Cited by 62 · see citing works
Felipe, C. G., Branquinho, J. L. D. O., Brandão, B. B., Guerra, B. A., Silva, I. D., Frontini, A., Thomou, T., Sartini, L., Cinti, S., Kahn, C. R., et al. (2016) · Aging · doi:10.18632/aging.100970 · Cited by 60 · see citing works
Self-citationHow does adipose tissue contribute to inflammageing?
Zamboni, M., Nori, N., Brunelli, A., & Zoico, E. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2020.111162 · Cited by 55 · see citing works
Cao, R., Fang, D., Wang, J., Yu, Y., Ye, H., Kang, P., Li, Z., Wang, H., & Gao, Q. F. (2019) · Journal of Diabetes Research · doi:10.1155/2019/4857921 · Cited by 55 · see citing works
Ефремова, А. В., Senzacqua, M., Venema, W., Isakov, E., Vincenzo, A. D., Zingaretti, M. C., Protasoni, M., Thomsky, M., Giordano, A., & Cinti, S. (2019) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-019-00721-4 · Cited by 52 · see citing works
Self-citationInsulin Resistance Is Cheerfully Hitched with Hypertension
Sinha, S., & Haque, M. (2022) · Life · doi:10.3390/life12040564 · Cited by 53 · see citing works
Molecular mechanism of crosstalk between immune and metabolic systems in metabolic syndrome
Hachiya, R., Tanaka, M., Itoh, M., & Suganami, T. (2022) · Inflammation and Regeneration · doi:10.1186/s41232-022-00198-7 · Cited by 44 · see citing works
Autologous Human Immunocompetent White Adipose Tissue‐on‐Chip
Rogal, J., Roosz, J., Teufel, C., Cipriano, M., Xu, R. F., Eisler, W., Weiß, M., Schenke‐Layland, K., & Loskill, P. (2022) · Advanced Science · doi:10.1002/advs.202104451 · Cited by 52 · see citing works
Regulation of immunometabolism in adipose tissue
Kumari, M., Heeren, J., & Scheja, L. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0668-3 · Cited by 52 · see citing works
Obesity and Pregnancy, the Perfect Metabolic Storm
Corrales, P., Vidal-Puig, A., & Medina-Gómez, G. (2021) · European Journal of Clinical Nutrition · doi:10.1038/s41430-021-00914-5 · Cited by 51 · see citing works
Adipose tissue plasticity and the pleiotropic roles of BMP signaling
Qian, S., Tang, Y., & Tang, Q. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100678 · Cited by 52 · see citing works
Ginsenoside Rb2 improves insulin resistance by inhibiting adipocyte pyroptosis
Lin, Y., Hu, Y., Hu, X., Yang, L., Chen, X., Li, Q., & Gu, X. (2020) · Adipocyte · doi:10.1080/21623945.2020.1778826 · Cited by 49 · see citing works
Zhuge, D., Javaid, H. M. A., Sahar, N.-E., Zhao, Y., & Huh, J. Y. (2020) · Archives of Pharmacal Research · doi:10.1007/s12272-020-01295-2 · Cited by 49 · see citing works
AGPAT2 is essential for postnatal development and maintenance of white and brown adipose tissue
Cautivo, K. M., Lizama, C. O., Tapía, P., Agarwal, A. K., Garg, A., Horton, J. D., & Cortés, V. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.05.004 · Cited by 48 · see citing works
Hunsche, C., Hernández, O., & la Fuente, M. D. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glv082 · Cited by 46 · see citing works
Annexins in Adipose Tissue: Novel Players in Obesity
Grewal, T., Enrich, C., Rentero, C., & Buechler, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143449 · Cited by 46 · see citing works
UCP1 protein: The molecular hub of adipose organ plasticity
Cinti, S. (2016) · Biochimie · doi:10.1016/j.biochi.2016.09.008 · Cited by 44 · see citing works
Self-citationKeskitalo, A., Munukka, E., Toivonen, R. K., Hollmén, M., Kainulainen, H., Huovinen, P., Jalkanen, S., & Pekkala, S. (2018) · PLoS ONE · doi:10.1371/journal.pone.0198262 · Cited by 44 · see citing works
A Lipid Perspective on Regulated Pyroptosis
Qiu, Y., Shi, Y., Zhu, N., Zhang, S., Zhang, C., Gu, J. L., He, P., Dai, A., & Li, Q. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.81017 · Cited by 40 · see citing works
Park, J., Huh, J. Y., Oh, J., Kim, J. I., Han, S. M., Shin, K. C., Jeon, Y. G., Choe, S. S., Park, J., & Kim, J. B. (2019) · Genes & Development · doi:10.1101/gad.329557.119 · Cited by 41 · see citing works
Acute high-fat feeding leads to disruptions in glucose homeostasis and worsens stroke outcome
Haley, M., Krishnan, S., Burrows, D., de Hoog, L., Thakrar, J., Schießl, I., Allan, S. M., & Lawrence, C. B. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17744718 · Cited by 39 · see citing works
Cimini, F. A., Barchetta, I., Ciccarelli, G., Leonetti, F., Silecchia, G., Chiappetta, C., Cristofano, C. D., Capoccia, D., Bertoccini, L., Ceccarelli, V., et al. (2020) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3358 · Cited by 39 · see citing works
- Authors
- Giordano, A., Murano, I., Mondini, E., Perugini, J., Smorlesi, A., Severi, I., Barazzoni, R., Scherer, P. E., & Cinti, S.
- Affiliations
- University of Trieste (IT)
- The University of Texas Southwestern Medical Center (US)
- Marche Polytechnic University (IT)
- Corresponding author
- Cinti, Saverio
- ORCID
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 54
- Issue
- 9
- Pages
- 2423-2436
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC3735940
- OpenAlex
- W1968144622
- Cited by
- 297
- References
- 52
- Citations by year
- 2026: 17 · 2025: 18 · 2024: 25 · 2023: 32 · 2022: 38 · 2021: 27 · 2020: 31 · 2019: 18 · 2018: 20 · 2017: 20 · 2016: 12 · 2015: 19 · 2014: 15 · 2013: 4
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Funders
- European Commission (278373)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- obesity, pyroptosis, NLRP3 inflammasome, caspase-1, white adipose tissue inflammation, crown-like structures, leptin deficiency, db/db mice, ob/ob mice, oxidative stress, reactive oxygen species, calcium accumulation, cholesterol crystals, adipocyte ultrastructure, visceral adipose tissue, subcutaneous adipose tissue, programmed cell death
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Female, Obesity, Ultrasonography, Cell Death, Adipocytes, Oxidative Stress, Leptin, Subcutaneous Fat, Intra-Abdominal Fat, Mice, Receptors, Leptin, Inflammasomes, Diet, High-Fat
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