The DOI matches its Crossref record; 44 of the 45 references it cites were found in a registry or an index.
A Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes: Role of Free Fatty Acids and Tumor Necrosis Factor α
Abstract
Objective— Weight gain is associated with infiltration of fat by macrophages, suggesting that they are an important source of inflammation in obese adipose tissue. Here we developed an in vitro coculture system composed of adipocytes and macrophages and examined the molecular mechanism whereby these cells communicate. Methods and Results— Coculture of differentiated 3T3-L1 adipocytes and macrophage cell line RAW264 results in the marked upregulation of proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), and the downregulation of the antiinflammatory cytokine adiponectin. Such inflammatory changes are induced by the coculture without direct contact, suggesting the role of soluble factors. A neutralizing antibody to TNF-α, which occurs mostly in macrophages, inhibits the inflammatory changes in 3T3-L1, suggesting that TNF-α is a major macrophage-derived mediator of inflammation in adipocytes. Conversely, free fatty acids (FFAs) may be important adipocyte-derived mediators of inflammation in macrophages, because the production of TNF-α in RAW264 is markedly increased by palmitate, a major FFA released from 3T3-L1. The inflammatory changes in the coculture are augmented by use of either hypertrophied 3T3-L1 or adipose stromal vascular fraction obtained from obese ob/ob mice. Conclusions— We postulate that a paracrine loop involving FFAs and TNF-α between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue.
Overview
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
Verification
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?
In the citing paper
“However, FFAs can also serve as ligands for the TLR4 complex (33), thereby activating the classical inflammatory response in the context of increased local extracellular lipid concentrations, which ultimately drives ATMΦ accumulation (34,35).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Plum, F. (1960) · Archives of Neurology · doi:10.1001/archneur.1960.03840090124020 · Cited by 10,388
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
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
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
Ford, E. S., Giles, W. H., & Dietz, W. H. (2002) · JAMA · doi:10.1001/jama.287.3.356 · Cited by 6,698
Grundy, S. M., Brewer, H. B., Cleeman, J. I., Smith, S. C., & Lenfant, C. (2004) · Circulation · doi:10.1161/01.cir.0000111245.75752.c6 · Cited by 5,982
Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L., & Spiegelman, B. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117936 · Cited by 3,543
Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.271.5249.665 · Cited by 2,630
‘Green mice’ as a source of ubiquitous green cells
Okabe, M., Ikawa, M., Kominami, K., Nakanishi, T., & Nishimune, Y. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00313-x · Cited by 2,581
Protection from obesity-induced insulin resistance in mice lacking TNF-α function
Uysal, K. T., Wiesbrock, S. M., Marino, M. W., & Hotamisligil, G. S. (1997) · Nature · doi:10.1038/39335 · Cited by 2,234
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
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728
Maeda, N., Takahashi, M., Funahashi, T., Kihara, S., Nishizawa, H., Kishida, K., Nagaretani, H., Matsuda, M., Komuro, R., Ouchi, N., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.9.2094 · Cited by 1,673
Gu, L., Okada, Y., Clinton, S. K., Gerard, C. J., Sukhova, G. K., Libby, P., & Rollins, B. J. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80139-2 · Cited by 1,574
Kern, P. A., Saghizadeh, M., Ong, J. M., Bosch, R. J., Deem, R., & Simsolo, R. B. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117899 · Cited by 1,305
Lee, J. Y., Sohn, K. H., Rhee, S. H., & Hwang, D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011695200 · Cited by 1,299
Monocyte chemoattractant protein 1 in obesity and insulin resistance
Sartipy, P., & Loskutoff, D. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1133870100 · Cited by 1,229
Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome
Fernández-Real, J. M., & Ricart, W. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0010 · Cited by 886
Minireview: Adiposity, Inflammation, and Atherogenesis
Lyon, C. J., Law, R. E., & Hsueh, W. A. (2003) · Endocrinology · doi:10.1210/en.2003-0285 · Cited by 761
Chemokines in the Pathogenesis of Vascular Disease
Charo, I. F., & Taubman, M. B. (2004) · Circulation Research · doi:10.1161/01.res.0000146672.10582.17 · Cited by 758
The perils of portliness: causes and consequences of visceral adiposity.
Montague, C. T., & O’Rahilly, S. (2000) · Diabetes · doi:10.2337/diabetes.49.6.883 · Cited by 735
Weight loss regulates inflammation‐related genes in white adipose tissue of obese subjects
ClÉment, K., Viguerie, N., Poitou, C., Carette, C., Pelloux, V., Curat, C. A., Sicard, A., Rome, S., Benis, A., Zucker, J., et al. (2004) · The FASEB Journal · doi:10.1096/fj.04-2204com · Cited by 640
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
Matsuzawa, Y., Funahashi, T., & Nakamura, T. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07793.x · Cited by 599
Lee, J. Y., Plakidas, A., Lee, W. H., Heikkinen, A., Chanmugam, P., Bray, G. A., & Hwang, D. H. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m200361-jlr200 · Cited by 557
Preadipocyte Conversion to Macrophage
Charrière, G. M., Cousin, B., Arnaud, E., André, M., Bacou, F., Pénicaud, L., & Casteilla, L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210811200 · Cited by 556
Bruun, J. M., Lihn, A. S., Pedersen, S. B., & Richelsen, B. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1696 · Cited by 555
Adiposity Elevates Plasma MCP-1 Levels Leading to the Increased CD11b-positive Monocytes in Mice
Takahashi, K., Mizuarai, S., Araki, H., Mashiko, S., Ishihara, A., Kanatani, A., Itadani, H., & Kotani, H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m309895200 · Cited by 327
Weigert, C., Brodbeck, K., Staiger, H., Kausch, C., Machicao, F., Häring, H. U., & Schleicher, E. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312692200 · Cited by 269
Mapping of Early Signaling Events in Tumor Necrosis Factor-α-mediated Lipolysis in Human Fat Cells
Rydén, M., Dicker, A., van Harmelen, V., Hauner, H., Brunnberg, M., Perbeck, L. G., Lönnqvist, F., & Arner, P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109498200 · Cited by 249
Souza, S. C., Palmer, H. J., Kang, Y., Yamamoto, M. T., Muliro, K. V., Paulson, K. E., & Greenberg, A. S. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10565 · Cited by 186
Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis
Yokoi, H., Mukoyama, M., Sugawara, A., Mori, K., Nagae, T., Makino, H., Suganami, T., Yahata, K., Fujinaga, Y., Tanaka, I., et al. (2002) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00122.2001 · Cited by 167
Self-citationAdipocyte differentiation induces dynamic changes in NF-κB expression and activity
Berg, A. H., Lin, Y., Lisanti, M. P., & Scherer, P. E. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00002.2004 · Cited by 160
Lipopolysaccharide stimulation of ERK1/2 increases TNF-α production via Egr-1
Shi, L., Kishore, R., McMullen, M. R., & Nagy, L. E. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00511.2001 · Cited by 147
Leptin Stimulates Ischemia-Induced Retinal Neovascularization
Suganami, E., Takagi, H., Ohashi, H., Suzuma, K., Suzuma, I., Oh, H., Watanabe, D., Ojima, T., Suganami, T., Fujio, Y., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.9.2443 · Cited by 141
Self-citation山内, 明., Kim, C., Li, S., Marchal, C. C., Towe, J., Atkinson, S. J., & Dinauer, M. C. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.10.5971 · Cited by 137
Ping, D., Jones, P. L., & Boss, J. M. (1996) · Immunity · doi:10.1016/s1074-7613(00)80412-4 · Cited by 126
Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells
Takaya, K., Koya, D., Isono, M., Sugimoto, T., Sugaya, T., Kashiwagi, A., & Haneda, M. (2003) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00230.2002 · Cited by 126
Kim, K.-Y., Kim, J. K., Jeon, J. H., Yoon, S. R., Choi, I., & Yang, Y. D. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.12.026 · Cited by 121
Comalada, M., Xaus, J., Valledor, A. F., López, C., Pennington, D. J., & Celada, A. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00228.2003 · Cited by 109
Augmented Expression of the obese Gene in the Adipose Tissue from Rats Fed High-Fat Diet
Masuzaki, H., Ogawa, Y., Hosoda, K., Kawada, T., Fushiki, T., & Nakao, K. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2631 · Cited by 86
Self-citationOverexpression of Brain Natriuretic Peptide in Mice Ameliorates Immune-Mediated Renal Injury
Suganami, T., Mukoyama, M., Sugawara, A., Mori, K., Nagae, T., Kasahara, M., Yahata, K., Makino, H., Fujinaga, Y., Ogawa, Y., et al. (2001) · Journal of the American Society of Nephrology · doi:10.1681/asn.v12122652 · Cited by 81
Self-citationPrevention and reversal of renal injury by leptin in a new mouse model of diabetic nephropathy
Suganami, T., Mukoyama, M., Mori, K., Yokoi, H., Koshikawa, M., Sawai, K., Hidaka, S., Ebihara, K., Tanaka, T., Sugawara, A., et al. (2004) · The FASEB Journal · doi:10.1096/fj.04-2183fje · Cited by 56
Self-citationYamamoto, Y., Yoshimasa, Y., Koh, M., Suga, J., Masuzaki, H., Ogawa, Y., Hosoda, K., Nishimura, H., Watanabe, Y., Inoue, G., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.3.332 · Cited by 39
Self-citation
Cited by
Sorted by citations
Nishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M., Otsu, M., Hara, K., Ueki, K., Sugiura, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.1964 · Cited by 2,230
Feuerer, M., Herrero, L., Cipolletta, D., Naaz, A., Wong, J., Nayer, A., Lee, J., Goldfine, A. B., Benoist, C., Shoelson, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.2002 · Cited by 2,145
Adipose tissue remodeling and obesity
Sun, K., Kusminski, C. M., & Scherer, P. E. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45887 · Cited by 1,941
Jung, U. J., & Choi, M. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15046184 · Cited by 1,971
“macrophages [29], thereby modulating inflammation of adipose tissue which contributes to obesity-associated metabolic complications.”
BackgroundAdipose tissue dysfunction in obesity, diabetes, and vascular diseases
Hajer, G. R., van Haeften, T. W., & Visseren, F. L. J. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn387 · Cited by 1,410
“Large adipocytes release more (saturated) FFAs which can bind to macrophage toll-like receptor-4 (TLR-4) resulting in NF-kB activation ultimately leading to augmented TNF-a production.(46,47) In turn, macrophage-derived TNF-a activates human adipocytes, thereby further inducing lipolysis and enhancing the expression o…”
Background
Metadata
- Authors
- Suganami, T., Nishida, J., & Ogawa, Y.
- Affiliations
- Tokyo Medical and Dental University (JP)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2005-10
- Volume
- 25
- Issue
- 10
- Pages
- 2062-2068
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2105448220
- Cited by
- 1,056
- References
- 45
- Citations by year
- 2026: 25 · 2025: 27 · 2024: 27 · 2023: 36 · 2022: 38 · 2021: 57 · 2020: 51 · 2019: 47 · 2018: 34 · 2017: 66 · 2016: 62 · 2015: 66 · 2014: 57 · 2013: 91 · 2012: 54
- FWCI
- 30.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Research Foundation for Clinical Pharmacology
- Ministry of Education, Culture, Sports, Science and Technology
- Novo Nordisk
- Smoking Research Foundation
- Kanae Foundation for the Promotion of Medical Science
- Mishima Kaiun Memorial Foundation
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- adipocytes, macrophages, paracrine signaling, adipose tissue inflammation, obesity, TNF-α, adiponectin, free fatty acids, palmitate, 3T3-L1 adipocytes, RAW264 macrophages, co-culture, ob/ob mice, adipose stromal vascular fraction, adipocyte hypertrophy
- MeSH terms
- Adipose Tissue, Animals, Cell Communication, Fatty Acids, Nonesterified, Gene Expression Regulation, Hypertrophy, Inflammation, Macrophages, Obesity, Tumor Necrosis Factor-alpha, Adipocytes, Coculture Techniques, Chemokine CCL2, Paracrine Communication, Metabolic Syndrome, 3T3-L1 Cells, Atherosclerosis, 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
