Adipocyte/macrophage fatty acid–binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice
Open accessAbstract
Adipose tissue inflammation is a characteristic of obesity. However, the mechanisms that regulate this inflammatory response and link adipose inflammation to systemic metabolic consequences are not fully understood. In this study, we have taken advantage of the highly restricted coexpression of adipocyte/macrophage fatty acid-binding proteins (FABPs) aP2 (FABP4) and mal1 (FABP5) to examine the contribution of these lipid chaperones in macrophages and adipocytes to local and systemic inflammation and metabolic homeostasis in mice. Deletion of FABPs in adipocytes resulted in reduced expression of inflammatory cytokines in macrophages, whereas the same deletion in macrophages led to enhanced insulin signaling and glucose uptake in adipocytes. Using radiation chimerism through bone marrow transplantation, we generated mice with FABP deficiency in bone marrow and stroma-derived elements in vivo and studied the impact of each cellular target on local and systemic insulin action and glucose metabolism in dietary obesity. The results of these experiments indicated that neither macrophages nor adipocytes individually could account for the total impact of FABPs on systemic metabolism and suggest that interactions between these 2 cell types, particularly in adipose tissue, are critical for the inflammatory basis of metabolic deterioration.
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.
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
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
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199 · 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
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
Kanda, H. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26498 · Cited by 2,682 · 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
Conditional gene targeting in macrophages and granulocytes using LysMcre mice
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R., & Förster, I. (1999) · Transgenic Research · doi:10.1023/a:1008942828960 · Cited by 2,143 · see citing works
Macrophage-specific PPARγ controls alternative activation and improves insulin resistance
Odegaard, J. I., Ricardo-Gonzalez, R. R., Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., Eagle, A. R., Vats, D., Brombacher, F., Ferrante, A. W., et al. (2007) · Nature · doi:10.1038/nature05894 · Cited by 2,107 · cited 1× · see citing works
“Similarly, specific and isolated deletion of target genes in the myeloid lineage has also produced support for the hypothesis that these cells impact systemic metabolic homeostasis (8, 9).”
BackgroundFatty acid-binding proteins: role in metabolic diseases and potential as drug targets
Furuhashi, M., & Hotamışlıgil, G. S. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2589 · Cited by 1,790 · see citing works
Self-citationIKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773 · see citing works
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., Charo, I., Leibel, R. L., & Jr., A. W. F. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335 · Cited by 1,497 · see citing works
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335c1 · Cited by 1,424 · see citing works
Kamei, N., Tobe, K., Suzuki, R., Ohsugi, M., Watanabe, T., Kubota, N., Ohtsuka-Kowatari, N., Kumagai, K., Sakamoto, K. Q., Kobayashi, M., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601284200 · Cited by 918 · see citing works
Hotamışlıgil, G. S., Johnson, R. S., Distel, R. J., Ellis, R., Papaioannou, V. E., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.274.5291.1377 · Cited by 917 · see citing works
Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2
Furuhashi, M., Tuncman, G., Görgün, C. Z., Makowski, L., Atsumi, G., Vaillancourt, E., Kono, K., Babaev, V. R., Fazio, S., Linton, M. F., et al. (2007) · Nature · doi:10.1038/nature05844 · Cited by 724 · see citing works
Self-citationMakowski, L., Boord, J. B., Maeda, K., Babaev, V. R., Uysal, K. T., Morgan, M. A., Parker, R. A., Suttles, J., Fazio, S., Hotamışlıgil, G. S., et al. (2001) · Nature Medicine · doi:10.1038/89076 · Cited by 687 · see citing works
Xu, A., Wang, Y., Xu, J. Y., Stejskal, D., Tam, S., Zhang, J., Wat, N. M. S., Wong, W. K., & Lam, K. S. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2005.062463 · Cited by 597 · see citing works
Solinas, G., Vilcu, C., Neels, J. G., Bandyopadhyay, G. K., Luo, J.-L., Naugler, W., Grivennikov, S., Wynshaw-Boris, A., Scadeng, M., Olefsky, J. M., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.011 · Cited by 513 · see citing works
Maeda, K., Cao, H., Kono, K., Görgün, C. Z., Furuhashi, M., Uysal, K. T., Cao, Q., Atsumi, G., Malone, H., Krishnan, B. S., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.008 · Cited by 478 · see citing works
Self-citationMakowski, L., Brittingham, K. C., Reynolds, J. M., Suttles, J., & Hotamışlıgil, G. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413788200 · Cited by 412 · see citing works
Hunt, C. R., Ro, J., Dobson, D. E., Min, H. Y., & Spiegelman, B. M. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.11.3786 · Cited by 329 · see citing works
Improved Glucose and Lipid Metabolism in Genetically Obese Mice Lacking aP2
Uysal, K. T., Scheja, L., Wiesbrock, S. M., Bonner‐Weir, S., & Hotamışlıgil, G. S. (2000) · Endocrinology · doi:10.1210/endo.141.9.7637 · Cited by 324 · see citing works
Coe, N. R., Simpson, M. A., & Bernlohr, D. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32133-7 · Cited by 297 · see citing works
Tuncman, G., Erbay, E., Hom, X., Vivo, I. D., Campos, H., Rimm, E. B., & Hotamışlıgil, G. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602178103 · Cited by 277 · see citing works
Self-citationCrossno, J. T., Majka, S. M., Grazia, T. J., Gill, R. G., & Klemm, D. J. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28510 · Cited by 268 · see citing works
Inouye, K. E., Shi, H., Howard, J. K., Daly, C. H., Lord, G. M., Rollins, B. J., & Flier, J. S. (2007) · Diabetes · doi:10.2337/db07-0425 · Cited by 252 · see citing works
Role of the Fatty Acid Binding Protein mal1 in Obesity and Insulin Resistance
Maeda, K., Uysal, K. T., Makowski, L., Görgün, C. Z., Atsumi, G., Parker, R. A., Brüning, J. C., Hertzel, A. V., Bernlohr, D., & Hotamışlıgil, G. S. (2003) · Diabetes · doi:10.2337/diabetes.52.2.300 · Cited by 224 · see citing works
Self-citationAltered insulin secretion associated with reduced lipolytic efficiency in aP2-/- mice.
Scheja, L., Makowski, L., Uysal, K. T., Wiesbrock, S. M., Shimshek, D. R., Meyers, D. S., Morgan, M. K., Parker, R. A., & Hotamışlıgil, G. S. (1999) · Diabetes · doi:10.2337/diabetes.48.10.1987 · Cited by 218 · see citing works
Boord, J. B., Maeda, K., Makowski, L., Babaev, V. R., Fazio, S., Linton, M. F., & Hotamışlıgil, G. S. (2004) · Circulation · doi:10.1161/01.cir.0000141735.13202.b6 · Cited by 193 · see citing works
Fu, Y., Luo, N., Lopes-Virella, M. F., & Garvey, W. T. (2002) · Atherosclerosis · doi:10.1016/s0021-9150(02)00305-2 · Cited by 185 · see citing works
The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation
Shum, B. O. V. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24767 · Cited by 153 · see citing works
Bone marrow–specific Cap gene deletion protects against high-fat diet–induced insulin resistance
Lesniewski, L. A., Hosch, S. E., Neels, J. G., de Luca, C., Pashmforoush, M., Lumeng, C. N.-K., Chiang, S.-H., Scadeng, M., Saltiel, A. R., & Olefsky, J. M. (2007) · Nature Medicine · doi:10.1038/nm1550 · Cited by 114 · see citing works
Koh, Y. J., Kang, S., Lee, H. J., Choi, T., Lee, H. S., Cho, C., & Koh, G. Y. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32504 · Cited by 90 · see citing works
Cao, H., Maeda, K., Görgün, C. Z., Kim, H., Park, S., Shulman, G. I., Kim, J. K., & Hotamışlıgil, G. S. (2006) · Diabetes · doi:10.2337/db05-1496 · Cited by 90 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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
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
Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association
Miller, M., Stone, N. J., Ballantyne, C., Bittner, V., Criqui, M. H., Ginsberg, H. N., Goldberg, A. C., Howard, W. J., Jacobson, M. S., Kris-Etherton, P. M., et al. (2011) · Circulation · doi:10.1161/cir.0b013e3182160726 · Cited by 1,871 · see citing works
Shin, N.-R., Lee, J.-C., Lee, H.-Y., Kim, M.-S., Whon, T. W., Lee, M.-S., & Bae, J.-W. (2014) · Gut · doi:10.1136/gutjnl-2012-303839 · Cited by 1,550 · see citing works
The cellular and signaling networks linking the immune system and metabolism in disease
Osborn, O., & Olefsky, J. M. (2012) · Nature Medicine · doi:10.1038/nm.2627 · Cited by 1,551 · see citing works
Normalization of obesity-associated insulin resistance through immunotherapy
Winer, S., Chan, Y., Paltser, G., Truong, D., Tsui, H., Bahrami, J., Dorfman, R., Wang, Y., Zielenski, J., Mastronardi, F., et al. (2009) · Nature Medicine · doi:10.1038/nm.2001 · Cited by 1,370 · see citing works
Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome
Maury, E., & Brichard, S. M. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.07.031 · Cited by 1,026 · see citing works
Lipolysis and lipid mobilization in human adipose tissue
Lafontan, M., & Langin, D. (2009) · Progress in Lipid Research · doi:10.1016/j.plipres.2009.05.001 · Cited by 825 · see citing works
Lee, B.-C., & Lee, J. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.017 · Cited by 697 · see citing works
Sampey, B. P., Vanhoose, A. M., Winfield, H. M., Freemerman, A. J., Muehlbauer, M. J., Fueger, P. T., Newgard, C. B., & Makowski, L. (2011) · Obesity · doi:10.1038/oby.2011.18 · Cited by 618 · see citing works
Kennedy, A. J., Martinez, K., Chuang, C., LaPoint, K., & McIntosh, M. (2008) · Journal of Nutrition · doi:10.3945/jn.108.098269 · Cited by 557 · see citing works
Foundations of Immunometabolism and Implications for Metabolic Health and Disease
Hotamışlıgil, G. S. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.009 · Cited by 515 · see citing works
Furuhashi, M., Saitoh, S., Shimamoto, K., & Miura, T. (2014) · Clinical Medicine Insights Cardiology · doi:10.4137/cmc.s17067 · Cited by 489 · see citing works
Self-citationErtunc, M. E., & Hotamışlıgil, G. S. (2016) · Journal of Lipid Research · doi:10.1194/jlr.r066514 · Cited by 485 · see citing works
Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus
Burhans, M. S., Hagman, D. K., Kuzma, J. N., Schmidt, K. A., & Kratz, M. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170040 · Cited by 427 · see citing works
Hodgson, K., Morris, J. L., Bridson, T. L., Govan, B., Rush, C. M., & Ketheesan, N. (2014) · Immunology · doi:10.1111/imm.12394 · Cited by 367 · see citing works
JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction
Solinas, G., & Karin, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-151340 · Cited by 347 · see citing works
Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication
Funcke, J., & Scherer, P. E. (2019) · Journal of Lipid Research · doi:10.1194/jlr.r094060 · Cited by 337 · see citing works
FABP4 Attenuates PPARγ and Adipogenesis and Is Inversely Correlated With PPARγ in Adipose Tissues
Garin-Shkolnik, T., Rudich, A., Hotamışlıgil, G. S., & Rubinstein, M. (2013) · Diabetes · doi:10.2337/db13-0436 · Cited by 334 · see citing works
Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases
Furuhashi, M. (2019) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.48710 · Cited by 324 · see citing works
Self-citationUltra-processed foods and human health: from epidemiological evidence to mechanistic insights
Srour, B., Kordahi, M. C., Bonazzi, E., Deschasaux, M., Touvier, M., & Chassaing, B. (2022) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(22)00169-8 · Cited by 326 · see citing works
Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis
Sung, H., Doh, K., Son, J. E., Park, J. G., Bae, Y., Choi, S., Nelson, S. M. L., Cowling, R. A., Nagy, K. V., Michael, I. P., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.010 · Cited by 299 · see citing works
Inflammation and endoplasmic reticulum stress in obesity and diabetes
Hotamışlıgil, G. S. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.238 · Cited by 285 · see citing works
Reconstruction of genome-scale metabolic models for 126 human tissues using mCADRE
Wang, Y., Eddy, J. A., & Price, N. D. (2012) · BMC Systems Biology · doi:10.1186/1752-0509-6-153 · Cited by 277 · see citing works
Adipocyte Lipid Chaperone aP2 Is a Secreted Adipokine Regulating Hepatic Glucose Production
Cao, H., Sekiya, M., Ertunc, M. E., Burak, M. F., Mayers, J. R., White, A., Inouye, K., Rickey, L., Erçal, B., Furuhashi, M., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.012 · Cited by 276 · see citing works
Self-citationMitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses
Chen, Y., Yang, M., Huang, W., Chen, W., Zhao, Y., Schulte, M. L., Volberding, P. J., Gerbec, Z. J., Zimmermann, M. T., Zeighami, A., et al. (2019) · Circulation Research · doi:10.1161/circresaha.119.315833 · Cited by 274 · see citing works
Adipocyte-Macrophage Cross-Talk in Obesity
Engin, A. B. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_14 · Cited by 269 · see citing works
Koliwad, S. K., Streeper, R. S., Monetti, M., Cornelissen, I., Chan, L. C., Terayama, K., Naylor, S. G., Rao, M., Hubbard, B. K., & Farese, R. V. (2010) · Journal of Clinical Investigation · doi:10.1172/jci36066 · Cited by 231 · see citing works
Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice
Lim, S., Honek, J., Xue, Y., Seki, T., Cao, Z., Andersson, P., Yang, X., Hosaka, K., & Cao, Y. (2012) · Nature Protocols · doi:10.1038/nprot.2012.013 · Cited by 228 · see citing works
Buckman, L. B., Hasty, A. H., Flaherty, D. K., Buckman, C. T., Thompson, M. M., Matlock, B. K., Weller, K., & Ellacott, K. L. J. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.06.007 · Cited by 216 · see citing works
Lamounier-Zepter, V., Look, C., Alvarez, J., Christ, T., Ravens, U., Schunck, W.-H., Ehrhart-Bornstein, M., Bornstein, S. R., & Morano, I. (2009) · Circulation Research · doi:10.1161/circresaha.109.200501 · Cited by 203 · see citing works
Adipokines: masterminds of metabolic inflammation
Tilg, H., Ianiro, G., Gasbarrini, A., & Adolph, T. E. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01103-8 · Cited by 219 · see citing works
Obesity, obstructive sleep apnoea and metabolic syndrome
LAM, J. C. M., MAK, J. C. W., & IP, M. S. M. (2012) · Respirology · doi:10.1111/j.1440-1843.2011.02081.x · Cited by 198 · see citing works
Wu, L., Parekh, V. V., Gabriel, C. L., Bracy, D. P., Marks–Shulman, P. A., Tamboli, R. A., Kim, S., Mendez-Fernandez, Y., Besra, G. S., Lomenick, J. P., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200498109 · Cited by 190 · see citing works
The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction
Packer, M. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.06.055 · Cited by 190 · see citing works
Milner, K., van der Poorten, D., Xu, A., Bugianesi, E., Kench, J. G., Lam, K. S. L., Chisholm, D. J., & George, J. (2009) · Hepatology · doi:10.1002/hep.22896 · Cited by 176 · see citing works
Macrophages and Adipocytes in Human Obesity
Capel, F., Klimčáková, E., Viguerie, N., Roussel, B., Šiklová, M., Kováčiková, M., Polak, J., Kováčová, Z., Galitzky, J., Maoret, J.-J., et al. (2009) · Diabetes · doi:10.2337/db09-0033 · Cited by 175 · see citing works
Adipokines, adiposity, and atherosclerosis
Liu, L., Shi, Z., Ji, X., Zhang, W., Luan, J., Zahr, T., & Qiang, L. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04286-2 · Cited by 175 · see citing works
The role of JAK–STAT signaling in adipose tissue function
Richard, A. J., & Stephens, J. M. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.030 · Cited by 169 · see citing works
Hypothalamic innate immune reaction in obesity
Kälin, S., Heppner, F. L., Bechmann, I., Prinz, M., Tschöp, M. H., & Yi, C.-X. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.48 · Cited by 167 · see citing works
Elmasri, H., Ghelfi, E., Yu, D. C. W., Traphagen, S., Cernadas, M., Cao, H., Shi, G., Plutzky, J., Şahin, M., Hotamışlıgil, G. S., et al. (2012) · Angiogenesis · doi:10.1007/s10456-012-9274-0 · Cited by 167 · see citing works
Self-citationThe immune system's involvement in obesity-driven type 2 diabetes
Shu, C. J., Benoist, C. O., & Mathis, D. J. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.12.001 · Cited by 165 · see citing works
Ishimura, S., Furuhashi, M., Watanabe, Y. S., Hoshina, K., Fuseya, T., Mita, T., Okazaki, Y., Koyama, M., Tanaka, M., Akasaka, H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081318 · Cited by 154 · see citing works
Self-citationIso, T., Maeda, K., Hanaoka, H., Suga, T., Goto, K., Syamsunarno, M. R. A. A., Hishiki, T., Nagahata, Y., Matsui, H., Arai, M., et al. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301588 · Cited by 148 · see citing works
Inhibition of Fatty Acid Binding Proteins Elevates Brain Anandamide Levels and Produces Analgesia
Kaczocha, M., Rebecchi, M. J., Ralph, B. P., Teng, Y.-H. G., Berger, W. T., Galbavy, W., Elmes, M. W., Glaser, S. T., Wang, L., Rizzo, R. C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094200 · Cited by 142 · see citing works
Role of macrophage tissue infiltration in obesity and insulin resistance
Bourlier, V., & Bouloumié, A. (2009) · Diabetes & Metabolism · doi:10.1016/j.diabet.2009.05.001 · Cited by 132 · see citing works
Role of fatty acid binding proteins (FABPs) in cancer development and progression
McKillop, I. H., Girardi, C. A., & Thompson, K. J. (2019) · Cellular Signalling · doi:10.1016/j.cellsig.2019.06.001 · Cited by 132 · see citing works
Johnson, A. R., Qin, Y., Cozzo, A. J., Freemerman, A. J., Huang, M. J., Zhao, L., Sampey, B. P., Milner, J. J., Beck, M. A., Damania, B., et al. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.04.005 · Cited by 130 · see citing works
FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women
Terra, X., Quintero, Y., Auguet, T., Porras, J. A., Hernández, M., Sabench, F., Aguilar, C., Luna, A. M., Déjardin, D. D. C., & Richart, C. (2011) · European Journal of Endocrinology · doi:10.1530/eje-10-1195 · Cited by 130 · see citing works
Eguchi, J., Kong, X., Tenta, M., Wang, X., Kang, S., & Rosen, E. D. (2013) · Diabetes · doi:10.2337/db12-1327 · Cited by 129 · see citing works
von Eynatten, M., Breitling, L. P., Roos, M., Baumann, M., Rothenbacher, D., & Brenner, H. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.248609 · Cited by 125 · see citing works
Furuhashi, M., Fuseya, T., Murata, M., Hoshina, K., Ishimura, S., Mita, T., Watanabe, Y. S., Omori, A., Matsumoto, M., Sugaya, T., et al. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.307225 · Cited by 124 · see citing works
Self-citationAdipocyte iron regulates leptin and food intake
Gao, Y. M., Li, Z., Gabrielsen, J. S., Simcox, J., Lee, S.-H., Jones, D., Cooksey, B., Stoddard, G. J., Cefalu, W. T., & McClain, D. A. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81860 · Cited by 127 · see citing works
Lipid Chaperones and Metabolic Inflammation
Furuhashi, M., Ishimura, S., Ota, H., & Miura, T. (2011) · International Journal of Inflammation · doi:10.4061/2011/642612 · Cited by 121 · see citing works
Self-citationModulation of endothelium function by fatty acids
Mallick, R., & Duttaroy, A. K. (2021) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-021-04260-9 · Cited by 119 · see citing works
Kolditz, C.-I., & Langin, D. (2010) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32833bed6a · Cited by 115 · see citing works
Mallick, R., Basak, S., & Duttaroy, A. K. (2021) · Progress in Lipid Research · doi:10.1016/j.plipres.2021.101116 · Cited by 117 · see citing works
Lipotoxicity in macrophages: evidence from diseases associated with the metabolic syndrome
Prieur, X., Rőszer, T., & Ricote, M. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.017 · Cited by 115 · see citing works
Rahman, S. M., Janssen, R. C., Choudhury, M., Baquero, K. C., Aikens, R. M., de la Houssaye, B. A., & Friedman, J. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.410613 · Cited by 114 · see citing works
Vallerie, S. N., Furuhashi, M., Fucho, R., & Hotamışlıgil, G. S. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003151 · Cited by 110 · see citing works
Self-citationCai, L., Wang, Z., Ji, A., Meyer, J. M., & van der Westhuyzen, D. R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036785 · Cited by 112 · see citing works
A role for novel adipose tissue‐secreted factors in obesity‐related carcinogenesis
Fernández, B. C., Andrade, S., Carreira, M. C., Casanueva, F. F., & Crujeiras, A. B. (2016) · Obesity Reviews · doi:10.1111/obr.12377 · Cited by 109 · see citing works
Xu, B., Chen, L., Zhan, Y., Marquez, K. N. S., Zhuo, L., Qi, S., Zhu, J., He, Y., Chen, X., Zhang, H., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.857919 · Cited by 108 · see citing works
Furuhashi, M., Ishimura, S., Ota, H., Hayashi, M., Nishitani, T., Tanaka, M., Yoshida, H., Shimamoto, K., Hotamışlıgil, G. S., & Miura, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027356 · Cited by 105 · see citing works
Self-citationCampión, J., Milagro, F. I., & Martínez, J. A. (2010) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-375003-7.00011-x · Cited by 104 · see citing works
Yan, F., Shen, N., Pang, J. X., Zhang, Y. W., Rao, E., Bode, A. M., Al‐Kali, A., Zhang, D., Litzow, M. R., Li, B., et al. (2016) · Leukemia · doi:10.1038/leu.2016.349 · Cited by 100 · see citing works
Ota, H., Furuhashi, M., Ishimura, S., Koyama, M., Okazaki, Y., Mita, T., Fuseya, T., Yamashita, T., Tanaka, M., Yoshida, H., et al. (2012) · American Journal of Hypertension · doi:10.1038/ajh.2012.88 · Cited by 101 · see citing works
Self-citationHou, Y., Wei, D., Zhang, Z., Guo, H., Li, S., Zhang, J., Zhang, P., Zhang, L., & Zhao, Y. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111668 · Cited by 100 · see citing works
Burak, M. F., Inouye, K., White, A., Lee, A., Tuncman, G., Calay, E. S., Sekiya, M., Tirosh, A., Eguchi, K., Birrane, G., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac6336 · Cited by 99 · see citing works
Self-citationPérez‐Pérez, R., Ortega, F. J., García‐Santos, E., López, J. A., Camafeita, E., Ricart, W., Fernández‐Real, J. M., & Peral, B. (2009) · Journal of Proteome Research · doi:10.1021/pr800942k · Cited by 97 · see citing works
Mita, T., Furuhashi, M., Hiramitsu, S., Ishii, J., Hoshina, K., Ishimura, S., Fuseya, T., Watanabe, Y. S., Tanaka, M., Ohno, K., et al. (2014) · Obesity · doi:10.1002/oby.20954 · Cited by 96 · see citing works
Self-citationLee, M. Y. K., Li, H., Xiao, Y., Zhou, Z., Xu, A., & Vanhoutte, P. M. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01158.x · Cited by 91 · see citing works
Identification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding Proteins
Hertzel, A. V., Hellberg, K., Reynolds, J. M., Kruse, A. C., Juhlmann, B. E., Smith, A. J., Sanders, M. A., Ohlendorf, D. H., Suttles, J., & Bernlohr, D. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900720m · Cited by 90 · see citing works
Immunological contributions to adipose tissue homeostasis
DiSpirito, J. R., & Mathis, D. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.10.005 · Cited by 88 · see citing works
“Notably, it has been shown that macrophages can secrete a soluble form of the fatty acid binding protein FABP4 (commonly known as aP2), and that macrophage-derived aP2 can worsen systemic insulin resistance by, in part, suppressing insulin-stimulated AKT phosphorylation and glucose uptake by adipocytes [42].”
Diabetic Cardiomyopathy: Current Approach and Potential Diagnostic and Therapeutic Targets
Gîlcă-Blanariu, G.-E., Ștefănescu, G., Bădulescu, O. V., Tănase, D. M., Bararu, I., & Ciocoiu, M. (2017) · Journal of Diabetes Research · doi:10.1155/2017/1310265 · Cited by 86 · see citing works
Fuseya, T., Furuhashi, M., Yuda, S., Muranaka, A., Kawamukai, M., Mita, T., Ishimura, S., Watanabe, Y. S., Hoshina, K., Tanaka, M., et al. (2014) · Cardiovascular Diabetology · doi:10.1186/s12933-014-0126-7 · Cited by 85 · see citing works
Self-citationChanges in adipose tissue macrophage and T cell during aging
Garg, S., Delaney, C. E., Shi, H., & Yung, R. (2014) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2013006833 · Cited by 78 · see citing works
Liu, W., Liu, Y., Lai, X., & Kuang, S. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.10.011 · Cited by 79 · see citing works
Ghelfi, E., Yu, D. C. W., Elmasri, H., Terwelp, M. D., Lee, C. G., Bhandari, V., COMHAIR, S. A. A., ERZURUM, S. C., Hotamışlıgil, G. S., Elias, J. A., et al. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.12.009 · Cited by 79 · see citing works
Relationship Between Obesity, Alzheimer’s Disease, and Parkinson’s Disease: an Astrocentric View
Martín-Jiménez, C., Gaitán-Vaca, D. M., Echeverrı́a, V., González, J., & Barreto, G. E. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0193-8 · Cited by 77 · see citing works
Regulation of adipose tissue lipolysis revisited
Bézaire, V., & Langin, D. (2009) · Proceedings of The Nutrition Society · doi:10.1017/s0029665109990279 · Cited by 77 · see citing works
Nicholls, H. T., Kowalski, G. M., Kennedy, D. J., Risis, S., Zaffino, L. A., Watson, N., Kanellakis, P., Watt, M. J., Bobik, A., Bonen, A., et al. (2011) · Diabetes · doi:10.2337/db10-1353 · Cited by 77 · see citing works
Wang, Y. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01528.x · Cited by 75 · see citing works
Exercise and Adipose Tissue Macrophages: New Frontiers in Obesity Research?
Goh, J., Goh, K. P., & Abbasi, A. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00065 · Cited by 73 · see citing works
Holm, S., Ueland, T., Dahl, T. B., Michelsen, A. E., Skjelland, M., Russell, D., Nymo, S. H., Krohg‐Sørensen, K., Clausen, O. P., Atar, D., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028785 · Cited by 73 · see citing works
Bagheri, R., Qasim, A., Mehta, N. N., Terembula, K., Kapoor, S. C., Braunstein, S. N., Schutta, M. H., Iqbal, N., Lehrke, M., & Reilly, M. P. (2010) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2010.06.028 · Cited by 72 · see citing works
Babaev, V. R., Runner, R. P., Fan, D., Ding, L., Zhang, Y., Tao, H., Erbay, E., Görgün, C. Z., Fazio, S., Hotamışlıgil, G. S., et al. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.225839 · Cited by 72 · see citing works
Self-citationSingh, D., Fox, S. M., Tal‐Singer, R., Plumb, J., Bates, S., Broad, P. M., Riley, J. W., Celli, B. R., & On behalf of the ECLIPSE Investigators (2011) · Thorax · doi:10.1136/thx.2010.153767 · Cited by 70 · see citing works
High expression of FABP4 and FABP6 in patients with colorectal cancer
Zhang, Y., Zhao, X., Deng, L., Li, X., Wang, G., Li, Y., & Chen, M. (2019) · World Journal of Surgical Oncology · doi:10.1186/s12957-019-1714-5 · Cited by 69 · see citing works
Goto, K., Iso, T., Hanaoka, H., Yamaguchi, A., Suga, T., Hattori, A., Irie, Y., Shinagawa, Y., Matsui, H., Syamsunarno, M. R. A. A., et al. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.112.004861 · Cited by 69 · see citing works
FABP7 upregulation induces a neurotoxic phenotype in astrocytes
Killoy, K. M., Harlan, B. A., Pehar, M., & Vargas, M. R. (2020) · Glia · doi:10.1002/glia.23879 · Cited by 67 · see citing works
The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity
Daemen, S., & Schilling, J. D. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03133 · Cited by 65 · see citing works
Autoimmune responses and inflammation in type 2 diabetes
Prasad, M., Chen, E. W., Toh, S.-A. E. S., & Gascoigne, N. R. J. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0220-243r · Cited by 65 · see citing works
Fatty Acids and their Proteins in Adipose Tissue Inflammation
Mallick, R., Basak, S., Das, R. K., Banerjee, A., Paul, S., Pathak, S., & Duttaroy, A. K. (2023) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-023-01185-6 · Cited by 66 · see citing works
Fuseya, T., Furuhashi, M., Matsumoto, M., Watanabe, Y. S., Hoshina, K., Mita, T., Ishimura, S., Tanaka, M., & Miura, T. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.006377 · Cited by 66 · see citing works
Self-citationContribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus
Burhans, M. S., Hagman, D. K., Kuzma, J. N., Schmidt, K. A., & Kratz, M. (2019) · Comprehensive physiology · doi:10.1002/j.2040-4603.2019.tb00055.x · Cited by 65 · see citing works
Boß, M., Kemmerer, M., Brüne, B., & Namgaladze, D. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.03.042 · Cited by 65 · see citing works
Adipokines in the treatment of diabetes mellitus and obesity
Catalán, V., Gómez‐Ambrosi, J., Rodrı́guez, A., Salvador, J., & Frühbeck, G. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560802618811 · Cited by 64 · see citing works
Powell, C. A., Nasser, M. W., Zhao, H., Wochna, J. C., Zhang, X., Shapiro, C. L., Shilo, K., & Ganju, R. K. (2015) · Oncotarget · doi:10.18632/oncotarget.3442 · Cited by 63 · see citing works
Song, J., Ren, P., Zhang, L., Wang, X. L., Chen, L., & Shen, Y. H. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.01.086 · Cited by 62 · see citing works
- Authors
- Furuhashi, M., Fucho, R., Görgün, C. Z., Tuncman, G., Cao, H., & Hotamisligil, G. S.
- Affiliations
- Harvard University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2008-06-01
- Volume
- 118
- Issue
- 7
- Pages
- 2640-50
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2423863
- OpenAlex
- W2025059877
- Semantic Scholar
- 006094a9303b57c51c4cf09b8015eafb6569c638
- Cited by
- 332
- References
- 34
- Citations by year
- 2025: 12 · 2024: 18 · 2023: 14 · 2022: 23 · 2021: 15 · 2020: 17 · 2019: 19 · 2018: 15 · 2017: 18 · 2016: 23 · 2015: 17 · 2014: 18 · 2013: 29 · 2012: 19
- FWCI
- 18.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- Iacocca Family Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL065405, HL 65405)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK52540, R90DK071507, P30DK040561, DK71507-04)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- fatty acid binding protein, FABP4, FABP5, adipose tissue inflammation, obesity, macrophages, adipocytes, insulin signaling, glucose uptake, inflammatory cytokines, bone marrow chimerism, metabolic homeostasis
- MeSH terms
- Adipose Tissue, Animals, Blood Glucose, Cell Communication, Glucose, Inflammation, Insulin, Liver, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Neoplasm Proteins, Obesity, Receptor, Insulin, Tumor Necrosis Factor-alpha, Bone Marrow Transplantation, Adipocytes, Mice, Knockout, Chemokine CCL2, Fatty Acid-Binding Proteins, Proto-Oncogene Proteins c-akt, Mice
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