Inflammation and the depot-specific secretome of human preadipocytes
Open accessAbstract
OBJECTIVE: Visceral white adipose tissue (WAT) expansion and macrophage accumulation are associated with metabolic dysfunction. Visceral WAT typically shows greater macrophage infiltration. Preadipocytes show varying proinflammatory expression profiles among WAT depots. The objective was to examine the secretomes and chemoattractive properties of preadipocytes from visceral and subcutaneous WAT. METHODS: A label-free quantitative proteomics approach was applied to study secretomes of subcutaneous and omental preadipocytes from obese subjects. Enzyme-linked immunosorbent assays and chemotaxis assays were used to confirm proinflammatory chemokine secretion between depots. RESULTS: Preadipocyte secretomes showed greater variation between depots than did intracellular protein expression. Chemokines were the most differentially secreted proteins. Omental preadipocytes induced chemoattraction of macrophages and monocytes. Neutralizing antibodies to the identified chemokines reduced macrophage/monocyte chemoattraction. Subcutaneous preadipocytes treated with interleukin-6 (IL-6) resembled omental preadipocytes in terms of chemokine secretion and macrophage/monocyte chemoattraction. Janus-activated kinase (JAK1/2) protein expression, which transduces IL-6 signaling, was higher in omental than subcutaneous preadipocytes and WAT. Inhibiting JAK in omental preadipocytes decreased chemokine secretion and macrophage/monocyte chemoattraction to levels closer to that observed in subcutaneous preadipocytes. CONCLUSIONS: Secretomes of omental and subcutaneous preadipocytes are distinct, with the former inducing more macrophage/monocyte chemoattraction, in part through IL-6/JAK-mediated signaling.
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?
Natural flavonoids such as quercetin and fisetin, used alone or with dasatinib, can promote senolysis in multiple in vitro and in vivo settings.
“The use of various natural flavonoids, including quercetin and fisetin, either alone or in combination with dasatinib, a pan-tyrosine kinase inhibitor, can stimulate senolysis in a variety of contexts in vitro and in vivo199,207–210.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [207]
The Results section on JAK inhibition reports changes in chemokine secretion and monocyte attraction by human preadipocytes, not senolysis. Searches for quercetin, fisetin, dasatinib, and senolytic effects found no passage addressing flavonoid-induced senolysis in vitro or in vivo; page numbers were unavailable in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measured
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
1 retracted
Aoki, N., Jinno, S., Nakagawa, Y., Asai, N., Arakawa, E., Tamura, N., Tamura, T., & Matsuda, T. (2007) · Endocrinology · doi:10.1210/en.2006-1479 · Cited by 162 · see citing works
RetractedThe metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481 · see citing works
Improved Prediction of Signal Peptides: SignalP 3.0
Dyrløv Bendtsen, J., Nielsen, H., von Heijne, G., & Brunak, S. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.05.028 · Cited by 6,350 · see citing works
Adipokines in inflammation and metabolic disease
Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011) · Nature Reviews Immunology · doi:10.1038/nri2921 · Cited by 4,625 · 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
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
Inflammation: the link between insulin resistance, obesity and diabetes
Dandona, P. (2004) · Trends in Immunology · doi:10.1016/j.it.2003.10.013 · Cited by 2,170 · see citing works
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · see citing works
Angiogenesis and Inflammation in Peritoneal Dialysis: The Role of Adipocytes
Shi, J., Yu, M., & Sheng, M. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000476017 · Cited by 1,403 · see citing works
Macrophage-mediated inflammation in metabolic disease
Chawla, A., Nguyen, K. D., & Goh, Y. P. S. (2011) · Nature reviews. Immunology · doi:10.1038/nri3071 · Cited by 1,314 · see citing works
Cancello, R., Henegar, C., Viguerie, N., Taleb, S., Poitou, C., Rouault, C., Coupaye, M., Pelloux, V., Hugol, D., Bouillot, J.-L., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2277 · Cited by 1,164 · see citing works
Fat tissue, aging, and cellular senescence
Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094 · see citing works
Self-citationAdipocyte 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
Carr, D. B., Utzschneider, K. M., Hull, R. L., Kodama, K., Retzlaff, B. M., Brunzell, J. D., Shofer, J. B., Fish, B. E., Knopp, R. H., & Kahn, S. E. (2004) · Diabetes · doi:10.2337/diabetes.53.8.2087 · Cited by 993 · see citing works
Mechanisms and Metabolic Implications of Regional Differences among Fat Depots
Tchkonia, T., Thomou, T., Zhu, Y. Z., Karagiannides, I., Pothoulakis, C., Jensen, M. D., & Kirkland, J. L. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.008 · Cited by 728 · see citing works
Self-citationBeneficial Effects of Subcutaneous Fat Transplantation on Metabolism
Tran, T. T., Yamamoto, Y., Gesta, S., & Kahn, C. R. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.04.004 · Cited by 705 · see citing works
Obesity, Regional Body Fat Distribution, and the Metabolic Syndrome in Older Men and Women
Goodpaster, B. H., Krishnaswami, S., Harris, T. B., Katsiaras, A., Kritchevsky, S. B., Simonsick, E. M., Nevitt, M., Holvoet, P., & Newman, A. B. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.7.777 · Cited by 637 · see citing works
Goodpaster, B. H., Krishnaswami, S., Resnick, H., Kelley, D. E., Haggerty, C., Harris, T. B., Schwartz, A. V., Kritchevsky, S., & Newman, A. B. (2003) · Diabetes Care · doi:10.2337/diacare.26.2.372 · Cited by 619 · see citing works
Cancello, R., Tordjman, J., Poitou, C., Guilhem, G., Bouillot, J. L., Hugol, D., Coussieu, C., Basdevant, A., Hen, A. B., Bedossa, P., et al. (2006) · Diabetes · doi:10.2337/db06-0133 · Cited by 607 · see citing works
From Blood Monocytes to Adipose Tissue-Resident Macrophages
Curat, C. A., Miranville, A., Sengenès, C., Diehl, M., Tonus, C., Busse, R., & Bouloumié, A. (2004) · Diabetes · doi:10.2337/diabetes.53.5.1285 · Cited by 600 · see citing works
Harman-Boehm, I., Blüher, M., Redel, H., Sion-Vardy, N., Ovadia, S., Avinoach, E., Shai, I., Klöting, N., Stumvoll, M., Bashan, N., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1811 · Cited by 574 · see citing works
Removal of Visceral Fat Prevents Insulin Resistance and Glucose Intolerance of Aging
Gabriely, I., Ma, X. H., Yang, X. M., Atzmon, G., Rajala, M. W., Berg, A. H., Scherer, P., Rossetti, L., & Barzilai, N. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2951 · Cited by 563 · see citing works
Adipose Tissue, Inflammation and Atherosclerosis
Gustafson, B. (2010) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.3939 · Cited by 466 · see citing works
Thörne, A., Lönnqvist, F., Apelman, J., Hellers, G., & Arner, P. (2002) · International Journal of Obesity · doi:10.1038/sj.ijo.0801871 · Cited by 462 · see citing works
Surgical removal of visceral fat reverses hepatic insulin resistance.
Barzilai, N., She, L., Liu, B. Q., Vuguin, P. M., Cohen, P., Wang, J., & Rossetti, L. (1999) · Diabetes · doi:10.2337/diabetes.48.1.94 · Cited by 373 · see citing works
Tchkonia, T., Lenburg, M. E., Thomou, T., Giorgadze, N., Frampton, G. M., Pirtskhalava, T., Cartwright, A., Cartwright, M., Flanagan, J. N., Karagiannides, I., et al. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00202.2006 · Cited by 349 · see citing works
Self-citationZeyda, M., & Stulnig, T. M. (2007) · Immunology Letters · doi:10.1016/j.imlet.2007.07.003 · Cited by 308 · see citing works
Fat depot origin affects adipogenesis in primary cultured and cloned human preadipocytes
Tchkonia, T., Giorgadze, N., Pirtskhalava, T., Tchoukalova, Y. D., Karagiannides, I., Forse, R. A., DePonte, M., Stevenson, M. T., Guo, W., Han, J., et al. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00653.2001 · Cited by 256 · see citing works
Self-citationAbdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus
Miyazaki, Y., Glass, L. C., Triplitt, C. L., Wajcberg, E., Mandarino, L. J., & DeFronzo, R. A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.0327.2001 · Cited by 251 · see citing works
Fat Depot–Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes
Tchkonia, T., Giorgadze, N., Pirtskhalava, T., Thomou, T., DePonte, M., Koo, A., Forse, R. A., Chinnappan, D., Martin-Ruiz, C. M., von Zglinicki, T., et al. (2006) · Diabetes · doi:10.2337/db06-0540 · Cited by 226 · see citing works
Self-citationThe Portal Theory Supported by Venous Drainage–Selective Fat Transplantation
Rytka, J. M., Wueest, S., Schoenle, E. J., & Konrad, D. (2010) · Diabetes · doi:10.2337/db10-0697 · Cited by 209 · see citing works
Fabbrini, E., Tamboli, R. A., Magkos, F., Marks–Shulman, P. A., Eckhauser, A. W., Richards, W. O., Klein, S., & Abumrad, N. N. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.04.056 · Cited by 207 · see citing works
Adipose Depots Possess Unique Developmental Gene Signatures
Yamamoto, Y., Gesta, S., Lee, K. Y., Tran, T. T., Saadatirad, P., & Kahn, C. R. (2010) · Obesity · doi:10.1038/oby.2009.512 · Cited by 185 · see citing works
Adipose tissue: A motor for the inflammation associated with obesity
Vachharajani, V., & Granger, D. N. (2009) · IUBMB Life · doi:10.1002/iub.169 · Cited by 151 · see citing works
Dunn, J. P., Abumrad, N. N., Breitman, I., Marks–Shulman, P. A., Flynn, C. R., Jabbour, K., Feurer, I. D., & Tamboli, R. A. (2011) · Diabetes Care · doi:10.2337/dc11-1383 · Cited by 111 · see citing works
Feng, D., Tang, Y., Kwon, H., Zong, H., Hawkins, M. A., Kitsis, R. N., & Pessin, J. E. (2011) · Diabetes · doi:10.2337/db10-1411 · Cited by 93 · see citing works
Tchoukalova, Y. D., Sarr, M. G., & Jensen, M. D. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00337.2004 · Cited by 84 · see citing works
Self-citationGreater Omentectomy Improves Insulin Sensitivity in Nonobese Dogs
Lottati, M., Kolka, C. M., Stefanovski, D., Kirkman, E. L., & Bergman, R. N. (2009) · Obesity · doi:10.1038/oby.2008.642 · Cited by 50 · see citing works
Zhang, H.-M., Chen, L., Wang, L., Xu, S., Wang, X., Yi, L.-L., Chen, D., Wu, Z., Zhang, J.-Y., Liao, Y.-F., et al. (2009) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2008.12.016 · Cited by 30 · see citing works
Self-citationLow-grade inflammation and depressive symptoms as predictors of abdominal obesity
Valtonen, M., Laaksonen, D. E., Laukkanen, J. A., Tolmunen, T., Viinamäki, H. T., Lakka, H., Lakka, T. A., NISKANEN, L. K., & Kauhanen, J. (2012) · Scandinavian Journal of Public Health · doi:10.1177/1403494812461730 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cellular senescence in ageing: from mechanisms to therapeutic opportunities
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00314-w · Cited by 2,277 · see citing works
Hickson, L. J., Langhi Prata, L. G. P., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., Herrmann, S. M., Jensen, M. D., Jia, Q., Jordan, K. L., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.08.069 · Cited by 1,383 · see citing works
Self-citationFranceschi, C., Garagnani, P., Vitale, G., Capri, M., & Salvioli, S. (2017) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.09.005 · Cited by 997 · see citing works
Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty
Stout, M. B., Justice, J. N., Nicklas, B. J., & Kirkland, J. L. (2017) · Physiology · doi:10.1152/physiol.00012.2016 · Cited by 272 · see citing works
Self-citationMetabolic adaptation in obesity and type ii diabetes: myokines, adipokines and hepatokines
Oh, K.-J., Lee, D., Kim, W., Han, B., Lee, S., & Bae, K.-H. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms18010008 · Cited by 210 · see citing works
The effects of myosteatosis on skeletal muscle function in older adults
Dondero, K., Friedman, B., Rekant, J., Landers‐Ramos, R., & Addison, O. (2024) · Physiological Reports · doi:10.14814/phy2.16042 · Cited by 63 · see citing works
Molecular pathology endpoints useful for aging studies
Niedernhofer, L. J., Kirkland, J. L., & Ladiges, W. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.012 · Cited by 59 · see citing works
Self-citation
- Authors
- Zhu, Y., Tchkonia, T., Stout, M. B., Giorgadze, N., Wang, L., Li, P. W., Heppelmann, C. J., Bouloumié, A., Jensen, M. D., Bergen, H. R., & Kirkland, J. L.
- Affiliations
- Mayo Clinic (US)
- Robert and Arlene Kogod Center on Aging; Mayo Clinic; Rochester Minnesota USA
- Université Toulouse III - Paul Sabatier (FR)
- Corresponding author
- Kirkland, James L.
- ORCID
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2015-04-10
- Volume
- 23
- Issue
- 5
- Pages
- 989-999
- ISSN
- 1930-7381 (ISSN-L)
- PMC
- PMC4414793
- OpenAlex
- W1514732199
- Cited by
- 42
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 3
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (AG31736, AG13925, AG41122, DK50456, DK40484)
- Ellison Foundation
- Inserm
- Noaber Foundation
- Ted Nash Foundation
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- preadipocytes, secretome, visceral adipose tissue, subcutaneous adipose tissue, omental adipose tissue, chemokines, monocytes, interleukin-6, adipose tissue inflammation
- MeSH terms
- Enzyme-Linked Immunosorbent Assay, Humans, Inflammation, Macrophages, Monocytes, Obesity, Omentum, Proteins, Interleukin-6, Subcutaneous Fat, Intra-Abdominal Fat, Adipocytes, White
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
