CXCL14, a Brown Adipokine that Mediates Brown-Fat-to-Macrophage Communication in Thermogenic Adaptation
Open accessAbstract
The beneficial effects of brown adipose tissue (BAT) are attributed to its capacity to oxidize metabolites and produce heat, but recent data suggest that secretory properties of BAT may also be involved. Here, we identify the chemokine CXCL14 (C-X-C motif chemokine ligand-14) as a novel regulatory factor secreted by BAT in response to thermogenic activation. We found that the CXCL14 released by brown adipocytes recruited alternatively activated (M2) macrophages. Cxcl14-null mice exposed to cold showed impaired BAT activity and low recruitment of macrophages, mainly of the M2 phenotype, into BAT. CXCL14 promoted the browning of white fat and ameliorated glucose/insulin homeostasis in high-fat-diet-induced obese mice. Impairment of type 2 cytokine signaling, as seen in Stat6-null mice, blunts the action of CXCL14, promoting adipose tissue browning. We propose that active BAT is a source of CXCL14, which concertedly promotes adaptive thermogenesis via M2 macrophage recruitment, BAT activation, and the browning of white fat.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
A transcriptomics data mining strategy identified CXCL14, a novel batokine that promotes thermogenesis by facilitating the recruitment of anti‐inflammatory macrophages to BAT.
“A similar approach, based on a transcriptomics data mining strategy, was used to identify CXCL14, a novel batokine that promotes thermogenesis by facilitating the recruitment of anti‐inflammatory macrophages to BAT 161.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [161]
Cites
Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433 · see citing works
Locating proteins in the cell using TargetP, SignalP and related tools
Emanuelsson, O., Brunak, S., von HEIJNE, G., & Nielsen, H. (2007) · Nature Protocols · doi:10.1038/nprot.2007.131 · Cited by 2,746 · see citing works
Adipose-derived circulating miRNAs regulate gene expression in other tissues
Thomou, T., Mori, M. A., Dreyfuss, J. M., Konishi, M., Sakaguchi, M., Wolfrum, C., Rao, T. N., Winnay, J. N., Garcia-Martin, R., Grinspoon, S. K., et al. (2017) · Nature · doi:10.1038/nature21365 · Cited by 1,539 · see citing works
Brown adipose tissue regulates glucose homeostasis and insulin sensitivity
Stanford, K. I., Middelbeek, R. J. W., Townsend, K. L., An, D., Nygaard, E. B., Hitchcox, K. M., Markan, K. R., Nakano, K., Hirshman, M. F., Tseng, Y.-H., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci62308 · Cited by 1,180 · see citing works
Feature-based prediction of non-classical and leaderless protein secretion
Bendtsen, J. D., Jensen, L. J., Blom, N., von HEIJNE, G., & Brunak, S. (2004) · Protein Engineering Design and Selection · doi:10.1093/protein/gzh037 · Cited by 1,179 · see citing works
Transcriptional Control of Brown Fat Determination by PRDM16
Seale, P., Kajimura, S., Yang, W., Chin, S., Rohas, L. M., Uldry, M., Tavernier, G., Langin, D., & Spiegelman, B. M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.06.001 · Cited by 1,174 · see citing works
Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis
Nguyen, K. D., Qiu, Y., Cui, X., Goh, Y. P. S., Mwangi, J., David, T., Mukundan, L., Brombacher, F., Locksley, R. M., & Chawla, A. (2011) · Nature · doi:10.1038/nature10653 · Cited by 1,038 · see citing works
Rao, R. R., Long, J. Z., White, J. P., Svensson, K. J., Lou, J., Lokurkar, I., Jedrychowski, M. P., Ruas, J. L., Wrann, C. D., Lo, J. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.065 · Cited by 973 · see citing works
Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity
Brestoff, J. R., Kim, B. S., Saenz, S. A., Stine, R. R., Monticelli, L. A., Sonnenberg, G. F., Thome, J. J., Farber, D. L., Lutfy, K., Seale, P., et al. (2015) · Nature · doi:10.1038/nature14115 · Cited by 968 · see citing works
Qiu, Y., Nguyen, K. D., Odegaard, J. I., Cui, X., Tian, X., Locksley, R. M., Palmiter, R. D., & Chawla, A. (2014) · Cell · doi:10.1016/j.cell.2014.03.066 · Cited by 869 · see citing works
Activated Type 2 Innate Lymphoid Cells Regulate Beige Fat Biogenesis
Lee, M.-W., Odegaard, J. I., Mukundan, L., Qiu, Y., Molofsky, A. B., Nussbaum, J. C., Yun, K. M., Locksley, R. M., & Chawla, A. (2014) · Cell · doi:10.1016/j.cell.2014.12.011 · Cited by 680 · see citing works
Brown adipose tissue as a secretory organ
Villarroya, F., Cereijo, R., Villarroya, J., & Giralt, M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.136 · Cited by 677 · see citing works
Self-citationThermogenic Activation Induces FGF21 Expression and Release in Brown Adipose Tissue
Hondares, E., Iglesias, R., Giralt, A., Gonzalez, F. J., Giralt, M., Mampel, T., & Villarroya, F. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.215889 · Cited by 623 · see citing works
Self-citationWhole-Genome Cartography of Estrogen Receptor α Binding Sites
Lin, C., Vega, V. B., Thomsen, J. S., Zhang, T., Kong, S. L., Xie, M., Chiu, K. P., Lipovich, L., Barnett, D., Stossi, F., et al. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030087 · Cited by 459 · see citing works
The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue
Lynes, M. D., Leiria, L. O., Lundh, M., Bartelt, A., Shamsi, F., Huang, T. L., Takahashi, H., Hirshman, M. F., Schlein, C., Lee, A., et al. (2017) · Nature Medicine · doi:10.1038/nm.4297 · Cited by 452 · see citing works
Microbiota depletion promotes browning of white adipose tissue and reduces obesity
Suárez-Zamorano, N., Fabbiano, S., Chevalier, C., Stojanović, O., Colin, D. J., Stevanović, A., Veyrat-Durebex, C., Tarallo, V., Rigo, D., Germain, S., et al. (2015) · Nature Medicine · doi:10.1038/nm.3994 · Cited by 403 · see citing works
Galić, S., Fullerton, M. D., Schertzer, J. D., Sikkema, S. R., Marcinko, K., Walkley, C. R., Izon, D. J., Honeyman, J. E., Chen, Z., van Denderen, B. J., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58577 · Cited by 344 · see citing works
Fischer, K., Ruiz, H. H., Jhun, K., Finan, B., Oberlin, D. J., van der Heide, V., Kalinovich, A., Petrovič, N., Wolf, Y., Clemmensen, C., et al. (2017) · Nature Medicine · doi:10.1038/nm.4316 · Cited by 326 · see citing works
Min, S. Y., Kady, J., Nam, M., Rojas-Rodriguez, R., Berkenwald, A., Kim, J. H., Noh, H. L., Kim, J. K., Cooper, M. P., Fitzgibbons, T. P., et al. (2016) · Nature Medicine · doi:10.1038/nm.4031 · Cited by 304 · see citing works
Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling
Fabbiano, S., Suárez-Zamorano, N., Rigo, D., Veyrat‐Durebex, C., Đokić, A., Colin, D., & Trajkovski, M. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.023 · Cited by 291 · see citing works
UCP1 mRNA does not produce heat
Nedergaard, J., & Cannon, B. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.01.009 · Cited by 264 · see citing works
Brown adipose tissue transplantation improves whole-body energy metabolism
Liu, X., Zheng, Z., Zhu, X., Meng, M., Li, L., Shen, Y., Chi, Q., Wang, D., Zhang, Z., Li, C., et al. (2013) · Cell Research · doi:10.1038/cr.2013.64 · Cited by 238 · see citing works
CXCL14 as an emerging immune and inflammatory modulator
Lu, J., Chatterjee, M., Schmid, H., Beck, S., & Gawaz, M. (2016) · Journal of Inflammation · doi:10.1186/s12950-015-0109-9 · Cited by 235 · see citing works
The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes
Quesada‐López, T., Cereijo, R., Turatsinze, J., Planavila, A., Cairó, M., Gavaldà‐Navarro, A., Peyrou, M., Moure, R., Iglesias, R., Giralt, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms13479 · Cited by 231 · see citing works
Self-citationToward an understanding of how immune cells control brown and beige adipobiology
Villarroya, F., Cereijo, R., Villarroya, J., Gavaldà-Navarro, A., & Giralt, M. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.04.006 · Cited by 198 · see citing works
Self-citationDisruption of CXC Motif Chemokine Ligand-14 in Mice Ameliorates Obesity-induced Insulin Resistance
Nara, N., Nakayama, Y., Okamoto, S., Tamura, H., Kiyono, M., Muraoka, M., Tanaka, K., Taya, C., Shitara, H., Ishii, R., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700412200 · Cited by 176 · see citing works
Inflammation and adipose tissue macrophages in lipodystrophic mice
Herrero, L., Shapiro, H., Nayer, A., Lee, J., & Shoelson, S. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905310107 · Cited by 158 · see citing works
Perinatal Licensing of Thermogenesis by IL-33 and ST2
Odegaard, J. I., Lee, M.-W., Sogawa, Y., Bertholet, A. M., Locksley, R. M., Weinberg, D. E., Kirichok, Y., Deo, R. C., & Chawla, A. (2016) · Cell · doi:10.1016/j.cell.2016.06.040 · Cited by 119 · see citing works
Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue
Duteil, D., Vukotić, M., Lausecker, F., Nenseth, H. Z., Müller, J. M., Urban, S., Willmann, D., Petroll, K., Messaddeq, N., Arrigoni, L., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.053 · Cited by 89 · see citing works
Lee, Y.-H., Kim, S.-N., Kwon, H.-J., Maddipati, K. R., & Granneman, J. G. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00355.2015 · Cited by 88 · see citing works
The Lives and Times of Brown Adipokines
Villarroya, F., Gavaldà‐Navarro, A., Peyrou, M., Villarroya, J., & Giralt, M. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.10.005 · Cited by 88 · see citing works
Self-citationGEPAS, a web-based tool for microarray data analysis and interpretation
Tárraga, J., Medina, I., Carbonell‐Caballero, J., Huerta‐Cepas, J., Mínguez, P., Alloza, E., Al‐Shahrour, F., Vegas-Azcárate, S., Götz, S., Escobar, P., et al. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn303 · Cited by 69 · see citing works
CXCL14 Deficiency in Mice Attenuates Obesity and Inhibits Feeding Behavior in a Novel Environment
Tanegashima, K., Okamoto, S., Nakayama, Y., Taya, C., Shitara, H., Ishii, R., Yonekawa, H., Minokoshi, Y., & Hara, T. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010321 · Cited by 48 · see citing works
Using gene expression to predict the secretome of differentiating human preadipocytes
Mutch, D. M., Rouault, C., Kéophiphath, M., Lacasa, D., & Clément, K. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.3 · Cited by 45 · see citing works
Takahashi, M., Takahashi, Y., Takahashi, K., Zolotaryov, F. N., Hong, K. S., Iida, K., Okimura, Y., Kaji, H., & Chihara, K. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.10.120 · Cited by 41 · see citing works
Liu, P.-S., Lin, Y.-W., Burton, F. H., et al. (2014) · Adipocyte · doi:10.4161/21623945.2014.981438 · Cited by 38 · see citing works
CXCL14: the Swiss army knife chemokine
Benarafa, C., & Wolf, M. (2015) · Oncotarget · doi:10.18632/oncotarget.6040 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The endocrine function of adipose tissues in health and cardiometabolic disease
Scheja, L., & Heeren, J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0230-6 · Cited by 663 · see citing works
Inter‐organ communication: a gatekeeper for metabolic health
Castillo‐Armengol, J., Fajas, L., & Lopez‐Mejia, I. C. (2019) · The EMBO Reports · doi:10.15252/embr.201947903 · Cited by 178 · see citing works
Ghesmati, Z., Rashid, M., Fayezi, S., Gieseler, F., Alizadeh, E., & Darabi, M. (2024) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09850-0 · Cited by 139 · see citing works
Obesity: A neuroimmunometabolic perspective
Larabee, C. M., Neely, O. C., & Domingos, A. I. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0283-6 · Cited by 123 · see citing works
Adipose tissue aging is regulated by an altered immune system
Zhang, Y.-X., Ou, M.-Y., Yang, Z.-H., Sun, Y., Li, Q.-F., & Zhou, S.-B. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1125395 · Cited by 62 · see citing works
Guo, Y., Zhang, Q., Yang, D., Chen, P., & Xiao, W. (2024) · Biomolecules · doi:10.3390/biom14030246 · Cited by 19 · see citing works
- Authors
- Cereijo, R., Gavaldà-Navarro, A., Cairó, M., Quesada-López, T., Villarroya, J., Morón-Ros, S., Sánchez-Infantes, D., Peyrou, M., Iglesias, R., Mampel, T., Turatsinze, J.-V., Eizirik, D. L., Giralt, M., & Villarroya, F.
- Affiliations
- Centro de Investigación Biomédica en Red (ES)
- Hospital de Sant Pau (ES)
- Hospital Sant Joan de Déu Barcelona (ES)
- Corresponding author
- Villarroya, Francesc
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 28
- Issue
- 5
- Pages
- 750-763.e6
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2886566773
- Cited by
- 236
- References
- 37
- Citations by year
- 2026: 23 · 2025: 24 · 2024: 27 · 2023: 45 · 2022: 34 · 2021: 34 · 2020: 28 · 2019: 20 · 2018: 1
- FWCI
- 14.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- WAT
- University of Barcelona
- Ministerio de Economia y Competitividad (SAF2017-85722R, PI17/00420)
- MINECO
- European Regional Development Fund
- ERDF
- Seventh Framework Program (FP7 BetaBat)
- Horizon 2020 Program (GA667191)
- National Council for Science and Technology in Mexico
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- CXCL14, brown adipose tissue, brown adipocytes, macrophage recruitment, M2 macrophages, thermogenesis, adaptive thermogenesis, white adipose tissue browning, cold exposure, obesity, STAT6, type 2 cytokines, adipokines, chemokines
- MeSH terms
- RAW 264.7 Cells, Adult, Animals, Adipose Tissue, Brown, Cells, Cultured, Energy Metabolism, Female, Glucose, Humans, Macrophages, Male, Mice, Inbred C57BL, Middle Aged, Obesity, Rats, Wistar, Chemokines, CXC, Thermogenesis, Mice, Adipocytes, Brown
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
