Immunological contributions to adipose tissue homeostasis
Open accessAbstract
Adipose tissue is composed of many functionally and developmentally distinct cell types, the metabolic core of which is the adipocyte. The classification of "adipocyte" encompasses three primary types - white, brown, and beige - with distinct origins, anatomic distributions, and homeostatic functions. The ability of adipocytes to store and release lipids, respond to insulin, and perform their endocrine functions (via secretion of adipokines) is heavily influenced by the immune system. Various cell populations of the innate and adaptive arms of the immune system can resist or exacerbate the development of the chronic, low-grade inflammation associated with obesity and metabolic dysfunction. Here, we discuss these interactions, with a focus on their consequences for adipocyte and adipose tissue function in the setting of chronic overnutrition. In addition, we will review the effects of diet composition on adipose tissue inflammation and recent evidence suggesting that diet-driven disruption of the gut microbiota can trigger pathologic inflammation of adipose tissue.
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?
The balance of pro- and anti-inflammatory signals is critical for disease progression in obese adipose tissue.
“The regulation of immune cell function and cytokine production in obese AT has been well studied (68), and it is now evident that the balance of pro-and antiinflammatory signals is critical for disease progression.”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [68]
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 · cited 1× · see citing works
“Infiltration of AT by macrophages was discovered in 2003, and for several years studies of this myeloid cell population dominated the field of immunometabolism [11,12].”
The 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
A core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823 · cited 1× · see citing works
“Especially salient to AT biology is the observation that obesity is associated with a less diverse biota in both humans and rodents [73,86].”
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 · cited 1× · see citing works
“inflammation (38), many groups have shown that TNFα is disruptive to insulin-stimulated: glucose”
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 · cited 1× · see citing works
“Infiltration of AT by macrophages was discovered in 2003, and for several years studies of this myeloid cell population dominated the field of immunometabolism [11,12].”
Chen, X., Xiu, M., Xing, J., Yu, S., Min, D., & Guo, F. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479439 · Cited by 5,759 · see citing works
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664 · cited 14× · see citing works
“A useful framework for discussing these populations is to distinguish cell types associated with maintaining metabolic health in the lean state and in early stages of DIO from those believed to initiate and/or exacerbate the chronic inflammation that contributes to adipocyte dysfunction in obesity.”
InfluentialAdipokines 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 · cited 1× · see citing works
“It is secreted almost exclusively by adipocytes and its levels in plasma are strongly correlated with insulin sensitivity and glucose tolerance [58].”
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
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 · cited 1× · see citing works
“In the decades since its discovery as a major mediator of diet-induced inflammation [38], many groups have shown that TNFα is disruptive to insulin-stimulated: glucose uptake, proteolytic activation of lipogenic gene expression, and induction of adipogenesis (reviewed in [39]).”
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690 · cited 1× · see citing works
“Despite the increased weight gain, TLR4-null mice are relatively glucose-tolerant and insulinsensitive [74].”
Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
Wu, J., Boström, P., Sparks, L. M., Li, Y., Choi, J. H., Giang, A.-H., Khandekar, M. J., Virtanen, K. A., Nuutila, P., Schaart, G., et al. (2012) · Cell · doi:10.1016/j.cell.2012.05.016 · Cited by 3,299 · cited 1× · see citing works
“When rodents are exposed to cold temperatures, or, notably, after prolonged high fat diet (HFD) feeding, beige adipocytes can dissipate heat in a manner similar to classical brown adipocytes [5].”
Kim, H. J., Park, S. Y., Choi, Y. J., Han, S. J., Lee, K. W., & Kim, D. J. (2013) · Hormone Research in Paediatrics · doi:10.1159/000348848 · Cited by 3,061 · see citing works
Turnbaugh, P. J., Bäckhed, F., Fulton, L., & Gordon, J. I. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.02.015 · Cited by 2,915 · cited 2× · see citing works
“Especially salient to AT biology is the observation that obesity is associated with a less diverse biota in both humans and rodents [73,86].”
Oh, D. Y., Talukdar, S., Bae, E. J., Imamura, T., Morinaga, H., Fan, W., Li, P., Lu, W. J., Watkins, S. M., & Olefsky, J. M. (2010) · Cell · doi:10.1016/j.cell.2010.07.041 · Cited by 2,428 · cited 1× · see citing works
“Triggering of GPR120 by n-3 PUFA suppresses NFκB and JNK signaling in macrophages and, importantly, this signaling is required for the robust insulinsensitizing effects of n-3 PUFA in vivo [81].”
What we talk about when we talk about fat
Rosen, E. D., & Spiegelman, B. M. (2014) · Cell · doi:10.1016/j.cell.2013.12.012 · Cited by 2,373 · cited 1× · see citing works
“Rather, we possess BAT-like thermogenic cells in the neck and supraclavicular regions [9].”
Brown and beige fat: Development, function and therapeutic potential
Harms, M., & Seale, P. (2013) · Nature Medicine · doi:10.1038/nm.3361 · Cited by 2,328 · cited 1× · see citing works
“Importantly, despite their lipogenic abilities, white, brown and beige adipocytes likely have distinct lineage ancestries (6,7) (Table1).”
Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes.
Guilherme, A., Virbasius, J. V., Puri, V., & Czech, M. P. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2391 · Cited by 2,292 · cited 1× · see citing works
“White adipocytes store lipid as triglycerides within unilocular droplets - a lipogenic pathway that is responsive to various stimuli, most notably insulin [1].”
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 · see citing works
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 · see citing works
Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression
Lord, G. M., Matarese, G., Howard, J. K., Baker, R. J., Bloom, S. R., & Lechler, R. I. (1998) · Nature · doi:10.1038/29795 · Cited by 2,150 · cited 1× · see citing works
“In combination with TCR triggering, leptin supports proliferation of activated T cells, likely through its upregulation of the glucose transporter Glut1 [53].”
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 · cited 2× · see citing works
“Importantly, systemic and AT-specific ablation of Tregs exacerbates diet-induced AT inflammation and metabolic dysfunction [25,28,29].”
Self-citationAdipose Tissue, Inflammation, and Cardiovascular Disease
Berg, A. H., & Scherer, P. E. (2005) · Circulation Research · doi:10.1161/01.res.0000163635.62927.34 · Cited by 2,113 · cited 1× · see citing works
“In adipocytes, signaling via TNFα or IL-6 can inhibit production of adiponectin [62].”
Michalek, R. D., Gerriets, V. A., Jacobs, S. R., Macintyre, A. N., MacIver, N. J., Mason, E. F., Sullivan, S. A., Nichols, A. G., & Rathmell, J. C. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003613 · Cited by 2,091 · cited 1× · see citing works
“Given recent findings on the preference of fatty acids (FA) as a fuel source for certain anti-inflammatory immunocytes, including Tregs and anti-inflammatory macrophages [48,49], it is interesting to consider whether these AT-resident immunocytes may secrete lipolytic cytokines to increase the local concentration of F…”
Diet-induced insulin resistance in mice lacking adiponectin/ACRP30
Maeda, N., Shimomura, I., Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., Furuyama, N., Kondo, H., Takahashi, M., Arita, Y., et al. (2002) · Nature Medicine · doi:10.1038/nm724 · Cited by 2,074 · cited 1× · see citing works
“Rodent gain- and loss-of-function models show that adiponectin levels are inversely correlated with the degree of AT inflammation [59].”
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 · cited 9× · see citing works
“The AT-resident B cell population in lean mice may be heterogeneous, as a second, distinct population of IL-10 producing antiinflammatory B cells has been found in VAT [24].”
InfluentialNormalization 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
Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation
Vats, D., Mukundan, L., Odegaard, J. I., Zhang, L., Smith, K. L., Morel, C. R., Greaves, D. R., Murray, P. J., & Chawla, A. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.011 · Cited by 1,369 · see citing works
Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose Homeostasis
Wu, D., Molofsky, A. B., Liang, H.-E., Ricardo-González, R. R., Jouihan, H. A., Bando, J. K., Chawla, A., & Locksley, R. M. (2011) · Science · doi:10.1126/science.1201475 · Cited by 1,361 · cited 2× · see citing works
“Importantly, gain- and loss-of-function studies have shown that Type 2 ILCs and eosinophils limit weight gain during HFD feeding and also promote glucose tolerance and insulin sensitivity, likely due in part to their effects on body weight [15,16].”
Tracking adipogenesis during white adipose tissue development, expansion and regeneration
Wang, Q. A., Tao, C., Gupta, R. K., & Scherer, P. E. (2013) · Nature Medicine · doi:10.1038/nm.3324 · Cited by 1,262 · cited 1× · see citing works
“Several studies support a role for macrophages in mediating HFD-induced adipocyte hyperplasia [67,68].”
Leptin regulates proinflammatory immune responses
Loffreda, S., Yang, S., Lin, H., Karp, C. L., Brengman, M. L., Wang, D., Klein, A. S., Bulkley, G. B., Bao, C., Noble, P. W., et al. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.1.57 · Cited by 1,251 · see citing works
PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells
Cipolletta, D., Feuerer, M., Li, A., Kamei, N., Lee, J., Shoelson, S. E., Benoist, C., & Mathis, D. (2012) · Nature · doi:10.1038/nature11132 · Cited by 1,143 · cited 1× · see citing works
“Importantly, systemic and VAT-specific ablation of Tregs exacerbates diet-induced AT inflammation and metabolic dysfunction (25,28,29).”
Self-citationAdipokines in health and disease
Fasshauer, M., & Blüher, M. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.04.014 · Cited by 1,050 · cited 1× · see citing works
“Hundreds of adipokines have been described [50], and we will limit discussion to those shown to have an effect on, or be affected by, immunocyte populations found in AT.”
Winer, D. A., Winer, S., Shen, L., Wadia, P. P., Yantha, J., Paltser, G., Tsui, H., Wu, P., Davidson, M. G., Alonso, M. N., et al. (2011) · Nature Medicine · doi:10.1038/nm.2353 · Cited by 1,050 · see citing works
Resistin, an Adipokine with Potent Proinflammatory Properties
Bokarewa, M. I., Nagaev, I., Dahlberg, L., Smith, U., & Tarkowski, A. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.9.5789 · Cited by 1,037 · cited 1× · see citing works
“Similar to leptin, its role in exacerbating AT inflammation is likely due, at least in part, to its ability to stimulate production of IL-6 and TNFα from macrophages [56,57].”
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 · cited 1× · see citing works
“After 8–12 weeks of HFD-feeding in rodents, the wave of adipogenesis that occurs in VAT is preceded by significant adipocyte cell death and formation of crownlike structures of macrophages that likely phagocytose dead adipocytes prior to their replacement with newly differentiated, smaller adipocytes [69].”
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
Caesar, R., Tremaroli, V., Kovatcheva-Datchary, P., Cani, P. D., & Bäckhed, F. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.026 · Cited by 960 · see citing works
Molofsky, A. B., Nussbaum, J. C., Liang, H.-E., Dyken, S. J. V., Cheng, L. E., Mohapatra, A., Chawla, A., & Locksley, R. M. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20121964 · Cited by 879 · cited 2× · see citing works
“Importantly, gain- and loss-of-function studies have shown that Type 2 ILCs and eosinophils limit weight gain during HFD feeding and also promote glucose tolerance and insulin sensitivity, likely due in part to their effects on body weight [15,16].”
Amar, J., Chabo, C., Waget, A., Klopp, P., Vachoux, C., Bermúdez‐Humarán, L. G., Smirnova, N. F., Bergé, M., Sulpice, T., Lahtinen, S. J., et al. (2011) · EMBO Molecular Medicine · doi:10.1002/emmm.201100159 · Cited by 837 · cited 1× · see citing works
“It has been reported that obese humans and HFD-fed rodents have circulating LPS levels that are two-to-three fold higher than that of their lean counterparts, a phenomenon termed “metabolic endotoxemia” (however, these LPS levels are still 10–50fold below those measured during a bacterial infection [87,88].”
Kratz, M., Coats, B. R., Hisert, K. B., Hagman, D. K., Mutskov, V. J., Peris, E., Schoenfelt, K. Q., Kuzma, J. N., Larson, I. A., Billing, P. S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.08.010 · Cited by 828 · cited 1× · see citing works
“This population secretes pro-inflammatory cytokines but is distinguished from classical M1 macrophages by expression of genes regulating lipid metabolism [22].”
Liu, J., Divoux, A., Sun, J., Zhang, J., Clément, K., Glickman, J. N., Sukhova, G. K., Wolters, P. J., Du, J., Gorgun, C. Z., et al. (2009) · Nature Medicine · doi:10.1038/nm.1994 · Cited by 796 · cited 2× · see citing works
“Macrophages, mast cells and neutrophils are three pro-inflammatory populations that accumulate in AT during DIO, with neutrophil influx observed after only a few days of HFD feeding [17,18].”
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 · cited 3× · see citing works
“The contribution of each process to DIO is an area of intense and ongoing debate [8].”
Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue
Kosteli, A., Sugaru, E., Haemmerle, G., Martin, J. F., Lei, J., Zechner, R., & Ferrante, A. W. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42845 · Cited by 726 · cited 1× · see citing works
“Rather, they functioned to suppress further adipocyte lipolysis [71].”
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 · cited 5× · see citing works
“In rodents, signaling through IL4Rα is required for maximal preadipocyte proliferation early in life and injection of IL-4 complexes is sufficient to stimulate the proliferation of beige preadipocytes [44].”
InfluentialDysfunction of lipid sensor GPR120 leads to obesity in both mouse and human
Ichimura, A., Hirasawa, A., Poulain‐Godefroy, O., Bonnefond, A., Hara, T., Yengo, L., Kimura, I., Leloire, A., Liu, N., Iida, K., et al. (2012) · Nature · doi:10.1038/nature10798 · Cited by 663 · cited 1× · see citing works
“Since this initial discovery, humans with lossof-function mutations in GPR120 have been identified and they are at increased risk for obesity and metabolic syndrome [82].”
Divoux, A., Tordjman, J., Lacasa, D., Veyrie, N., Hugol, D., Aissat, A., Basdevant, A., Guerre-Millo, M., Poitou, C., Zucker, J., et al. (2010) · Diabetes · doi:10.2337/db10-0585 · Cited by 620 · cited 9× · see citing works
“The AT-resident B cell population in lean mice may be heterogeneous, as a second, distinct population of IL-10 producing antiinflammatory B cells has been found in VAT [24].”
InfluentialHuman Leptin Stimulates Proliferation and Activation of Human Circulating Monocytes
Santos‐Álvarez, J., Goberna, R., & Sánchez‐Margalet, V. (1999) · Cellular Immunology · doi:10.1006/cimm.1999.1490 · Cited by 600 · see citing works
Kumada, M., Kihara, S., Ouchi, N., Kobayashi, H., Okamoto, Y., Ohashi, K., Maeda, K., Nagaretani, H., Kishida, K., Maeda, N., et al. (2004) · Circulation · doi:10.1161/01.cir.0000127953.98131.ed · Cited by 555 · cited 6× · see citing works
“The AT-resident B cell population in lean mice may be heterogeneous, as a second, distinct population of IL-10 producing antiinflammatory B cells has been found in VAT [24].”
InfluentialZeyda, M., Farmer, D., Todoric, J., Aszmann, O. C., Speiser, M., Györi, G., Zlabinger, G. J., & Stulnig, T. M. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803632 · Cited by 553 · cited 1× · see citing works
“Several studies have refined this model [20,21], including the recent description of “metabolically activated” macrophages that accumulate in AT during DIO and can be induced by a cocktail of metabolic stimuli (insulin, glucose and the saturated fatty acid palmitate).”
Interferon-γ, a Th1 Cytokine, Regulates Fat Inflammation
Rocha, V. Z., Folco, E. J. E., Sukhova, G. K., Shimizu, K., Gotsman, I., Vernon, A. H., & Libby, P. (2008) · Circulation Research · doi:10.1161/circresaha.108.177105 · Cited by 524 · see citing works
Xu, X., Grijalva, A., Skowronski, A., van Eijk, M., Serlie, M. J., & Ferrante, A. W. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.11.001 · Cited by 523 · cited 1× · see citing works
“Several studies have refined this model [20,21], including the recent description of “metabolically activated” macrophages that accumulate in AT during DIO and can be induced by a cocktail of metabolic stimuli (insulin, glucose and the saturated fatty acid palmitate).”
DeFuria, J., Belkina, A. C., Jagannathan-Bogdan, M., Snyder-Cappione, J., Carr, J. D., Nersesova, Y. R., Markham, D., Strissel, K. J., Watkins, A. A., Zhu, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215840110 · Cited by 521 · cited 1× · see citing works
“B cells also have a proinflammatory, metabolically deleterious role in AT inflammation, as shown by DIO studies in B cell-deficient mice [33,34].”
Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding
Elgazar-Carmon, V., Rudich, A., Hadad, N., & Lévy, R. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800132-jlr200 · Cited by 488 · see citing works
A Smooth Muscle-Like Origin for Beige Adipocytes
Long, J. Z., Svensson, K. J., Tsai, L. T.-Y., Zeng, X., Roh, H. C., Kong, X., Rao, R. R., Lou, J., Lokurkar, I. A., Baur, W. E., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.025 · Cited by 462 · see citing works
The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes
Vitali, A., Murano, I., Zingaretti, M. C., Frontini, A., Ricquier, D., & Cinti, S. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m018846 · Cited by 461 · see citing works
Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro
Kaser, S., Kaser, A., Sandhofer, A., Ebenbichler, C. F., Tilg, H., & Patsch, J. R. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.07.003 · Cited by 460 · cited 1× · see citing works
“Similar to leptin, its role in exacerbating AT inflammation is likely due, at least in part, to its ability to stimulate production of IL-6 and TNFα from macrophages [56,57].”
The gut microbiota in human energy homeostasis and obesity
Rosenbaum, M., Knight, R., & Leibel, R. L. (2015) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.07.002 · Cited by 450 · cited 1× · see citing works
“Microbial symbionts colonizing the human gastrointestinal tract are implicated in regulating several aspects of energy balance, including satiety, energy expenditure, fat storage and extraction of calories from the diet [84,85].”
Immunological Goings-on in Visceral Adipose Tissue
Mathis, D. J. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.008 · Cited by 433 · cited 1× · see citing works
“Twelve years later, the roll call of immunocyte populations found as resident within, or diet-driven to, AT depots reads like a census of almost all known myeloid and lymphoid subsets [13].”
Self-citationThe Changed Metabolic World with Human Brown Adipose Tissue: Therapeutic Visions
Nedergaard, J., & Cannon, B. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.007 · Cited by 426 · cited 5× · see citing works
“The interscapular BAT depot of humans is most prominent in infants, while adults have uncoupling-competent adipocyte clusters in the neck region.”
InfluentialIL-17 regulates adipogenesis, glucose homeostasis, and obesity
Zúñiga, L. A., Shen, W.-J., Joyce-Shaikh, B., Pyatnova, E. A., Richards, A. G., Thom, C., Andrade, S. M., Cua, D. J., Kraemer, F. B., & Butcher, E. C. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001269 · Cited by 394 · cited 1× · see citing works
“Two other pro-inflammatory cytokines, IFNγ and IL-17, have a similar effect, with all three likely suppressing the core transcriptional cascade required for pre-adipocyte differentiation [35,41,43].”
Lynch, L., Michelet, X., Zhang, S., Brennan, P. J., Moseman, E. A., Lester, C., Besra, G. S., Vomhof‐DeKrey, E. E., Tighe, M., Koay, H., et al. (2014) · Nature Immunology · doi:10.1038/ni.3047 · Cited by 387 · see citing works
Modulation of adipose tissue inflammation by bioactive food compounds
Siriwardhana, N., Kalupahana, N. S., Cekanova, M., LeMieux, M. J., Greer, B. P., & Moustaïd‐Moussa, N. (2013) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2012.12.013 · Cited by 345 · cited 1× · see citing works
“obesigenic, which needs to be considered as a primary mechanism for their antiinflammatory effects in AT [78,79].”
Tlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat
Davis, J. E., Gabler, N. K., Walker‐Daniels, J., & Spurlock, M. E. (2008) · Obesity · doi:10.1038/oby.2008.210 · Cited by 334 · see citing works
Furuhashi, M., Fucho, R., Görgün, C. Z., Tuncman, G., Cao, H., & Hotamisligil, G. S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34750 · Cited by 332 · cited 1× · 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].”
Caesar, R., Reigstad, C. S., Bäckhed, H. K., Reinhardt, C., Ketonen, M., Östergren‐Lundén, G., Cani, P. D., & Bäckhed, F. (2012) · Gut · doi:10.1136/gutjnl-2011-301689 · Cited by 330 · cited 1× · see citing works
“Interestingly, LPS immunogenicity is not required for increased fat mass in GF mice, but is required for macrophage accumulation in AT [89], suggesting that microbiota-derived LPS could potentiate immunocyte infiltration into AT.”
Involvement of tissue bacteria in the onset of diabetes in humans: evidence for a concept
for the D.E.S.I.R. Study Group, Amar, J., Sérino, M., Lange, C., Chabo, C., Iacovoni, J. S., Mondot, S., Lepage, P., Klopp, C., Mariette, J., et al. (2011) · Diabetologia · doi:10.1007/s00125-011-2329-8 · Cited by 327 · cited 1× · see citing works
“It has been reported that obese humans and HFD-fed rodents have circulating LPS levels that are two-to-three fold higher than that of their lean counterparts, a phenomenon termed “metabolic endotoxemia” (however, these LPS levels are still 10–50fold below those measured during a bacterial infection [87,88].”
Ruzickova, J., Rossmeisl, M., Prazak, T., Flachs, P., Sponarova, J., Vecka, M., TVRZICKÁ, E., Bryhn, M., & Kopecký, J. (2004) · Lipids · doi:10.1007/s11745-004-1345-9 · Cited by 327 · cited 1× · see citing works
“obesigenic, which needs to be considered as a primary mechanism for their antiinflammatory effects in AT [78,79].”
Eller, K., Kirsch, A. H., Wolf, A. M., Sopper, S., Tagwerker, A., Stanzl, U., Wolf, D. G. F., Patsch, W., Rosenkranz, A. R., & Eller, P. (2011) · Diabetes · doi:10.2337/db11-0358 · Cited by 318 · see citing works
Deiuliis, J. A., Shah, Z., Shah, N., NEEDLEMAN, B. J., Mikami, D. J., Narula, V. K., Perry, K. A., Hazey, J. W., Kampfrath, T., Kollengode, M. S., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016376 · Cited by 314 · see citing works
Kalupahana, N. S., Claycombe, K., Newman, S. J., Stewart, T. P., Siriwardhana, N., Matthan, N. R., Lichtenstein, A. H., & Moustaïd‐Moussa, N. (2010) · Journal of Nutrition · doi:10.3945/jn.110.125732 · Cited by 301 · cited 1× · see citing works
“Notably, if EPA is used therapeutically, after 6 weeks of HFD feeding, it still improves glucose tolerance [80].”
Abdominal obesity: a marker of ectopic fat accumulation
Smith, U. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81507 · Cited by 298 · cited 1× · see citing works
“Functionally, AT depots differ in progenitor proliferation rates, lipogenic and lipolytic capacity, and adipokine secretion profiles [10].”
Human resistin: found in translation from mouse to man
Schwartz, D. R., & Lazar, M. A. (2011) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.03.005 · Cited by 297 · cited 1× · see citing works
“Resistin is an especially interesting proinflammatory adipokine because of its species-specific regulation, being produced by adipocytes in rodents but predominantly by macrophages in humans [55].”
Xue, B., Rim, J.-S., Hogan, J. C., Coulter, A. A., Koza, R. A., & Kozak, L. P. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m600287-jlr200 · Cited by 288 · cited 1× · see citing works
“Excitingly, the brown/white paradigm has been revised by the discovery of beige (also known as brite) adipocytes dispersed within WAT depots [3,4].”
Identification of an Adipogenic Niche for Adipose Tissue Remodeling and Restoration
Lee, Y., Petkova, A. P., & Granneman, J. G. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.003 · Cited by 274 · cited 2× · see citing works
“An attractive idea is that macrophages play a similar role in HFD-induced hyperplasia, and while the pattern of crown-like structure formation is similar in the two models (70), further experiments will be needed to determine whether similar macrophage-driven adipogenesis”
Insulin signalling mechanisms for triacylglycerol storage
Czech, M., Tencerová, M., Pedersen, D. J., & Aouadi, M. (2013) · Diabetologia · doi:10.1007/s00125-013-2869-1 · Cited by 272 · see citing works
Microbial modulation of insulin sensitivity
Khan, M. T., Nieuwdorp, M., & Bäckhed, F. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.006 · Cited by 260 · cited 1× · see citing works
“Microbial symbionts colonizing the human gastrointestinal tract are implicated in regulating several aspects of energy balance, including satiety, energy expenditure, fat storage and extraction of calories from the diet [84,85].”
Adiponectin inhibits Toll‐like receptor family‐induced signaling
Yamaguchi, N., Argueta, J. G. M., Masuhiro, Y., Kagishita, M., Nonaka, K., Saito, T., Hanazawa, S., & Yamashita, Y. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.11.019 · Cited by 259 · cited 6× · see citing works
“The AT-resident B cell population in lean mice may be heterogeneous, as a second, distinct population of IL-10 producing antiinflammatory B cells has been found in VAT [24].”
InfluentialSaturated Fatty Acids Do Not Directly Stimulate Toll-Like Receptor Signaling
Erridge, C., & Samani, N. J. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.194050 · Cited by 258 · see citing works
McGillicuddy, F. C., Chiquoine, E. H., Hinkle, C. C., Kim, R. J., Shah, R. D., Roche, H. M., Smyth, E. M., & Reilly, M. P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.061655 · Cited by 255 · see citing works
Adipose natural regulatory B cells negatively control adipose tissue inflammation
Nishimura, S., Manabe, I., Takaki, S., Nagasaki, M., Otsu, M., Yamashita, H., Sugita, J., Yoshimura, K., Eto, K., Komuro, I., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.017 · Cited by 251 · cited 9× · see citing works
“The AT-resident B cell population in lean mice may be heterogeneous, as a second, distinct population of IL-10 producing antiinflammatory B cells has been found in VAT [24].”
Influential20 YEARS OF LEPTIN: Leptin at 20: an overview
Friedman, J. M. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0405 · Cited by 249 · cited 1× · see citing works
“Leptin is an adipokine that exerts its most profound actions via CNS regulation of feeding behavior, where it promotes satiety and prevents weight gain (51).”
Kim, S. M., Lun, M., Wang, M., Senyo, S. E., Guillermier, C., Patwari, P., & Steinhauser, M. L. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.010 · Cited by 244 · cited 1× · see citing works
“Several studies support a role for macrophages in mediating HFD-induced adipocyte hyperplasia [67,68].”
Interplay Between Human Adipocytes and T Lymphocytes in Obesity
Duffaut, C., Zakaroff‐Girard, A., Bourlier, V., Decaunes, P., Maumus, M., Chiotasso, P., Sengenès, C., Lafontan, M., Galitzky, J., & Bouloumié, A. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.192583 · Cited by 232 · cited 1× · see citing works
“More recent studies have demonstrated similar deleterious effects of IFNγ and IL-17 on adipocytes [40,41].”
Innate sensors of pathogen and stress: Linking inflammation to obesity
Jin, C., & Flavell, R. A. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.06.022 · Cited by 195 · cited 1× · see citing works
“An alternative and intriguing hypothesis to ligation of TLR4 by SFAs centers on obesity-associated dysregulation of the gut microbiota, which can result in elevated systemic LPS that is sufficient to trigger TLR signaling in AT [77].”
Mast Cells in Human Adipose Tissue: Link with Morbid Obesity, Inflammatory Status, and Diabetes
Divoux, A., Moutel, S., Poitou, C., Lacasa, D., Veyrie, N., Aissat, A., Arock, M., Guerre-Millo, M., & Clément, K. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1532 · Cited by 187 · cited 1× · see citing works
“Interestingly, in humans, mast cells preferentially accumulate in visually distinct fibrotic bundles within visceral and subcutaneous depots of individuals with Type 2 diabetes [66], and their abundance is positively correlated with fibrosis, macrophage accumulation and endothelial cell inflammation.”
Vila, I. K., Badin, P.-M., Marques, M.-A., Monbrun, L., Lefort, C., Mir, L., Louche, K., Bourlier, V., Roussel, B., Gui, P., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.062 · Cited by 165 · cited 1× · see citing works
“Notably, this response requires expression of TLR4 on bone-marrow-derived cells, suggesting that resident immunocytes promote HFD-induced AT fibrosis [65].”
Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis
Tsao, C.-H., Shiau, M., Chuang, P.-H., Chang, Y.-H., & Hwang, J. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m041392 · Cited by 149 · cited 1× · see citing works
“signaling pathways associated with resistance to DIO and dampening of AT inflammation, such as IL-4, can also induce lipolysis (47).”
Fat in flames: influence of cytokines and pattern recognition receptors on adipocyte lipolysis
Grant, R. W., & Stephens, J. M. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00053.2015 · Cited by 105 · see citing works
Xu, H., Hirosumi, J., Uysal, K. T., Güler, A. D., & Hotamışlıgil, G. S. (2002) · Endocrinology · doi:10.1210/endo.143.4.8715 · Cited by 92 · see citing works
Role of hormone-sensitive lipase in β-adrenergic remodeling of white adipose tissue
Mottillo, E. P., Shen, X., & Granneman, J. G. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00051.2007 · Cited by 84 · see citing works
Wu, L., Parekh, V. V., Hsiao, J., Kitamura, D., & Kaer, L. V. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1324052111 · Cited by 70 · cited 9× · see citing works
“The AT-resident B cell population in lean mice may be heterogeneous, as a second, distinct population of IL-10 producing antiinflammatory B cells has been found in VAT [24].”
InfluentialType 2 responses at the interface between immunity and fat metabolism
Odegaard, J. I., & Chawla, A. (2015) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.07.003 · Cited by 55 · cited 1× · see citing works
“In lean humans and rodents, AT macrophages may promote tissue remodeling and temper inflammation by secreting anti-inflammatory cytokines [14].”
Monk, J. M., Liddle, D. M., Boer, A. A. D., Brown, M. J., Power, K. A., David, W. L., & Robinson, L. E. (2015) · Journal of Nutrition · doi:10.3945/jn.114.205443 · Cited by 45 · cited 1× · see citing works
“In the lymphocyte compartment, supplementation of rodent diets with fish oil ameliorates the pro-inflammatory effects of CD8+ T cells on cultured adipocytes, suppressing NFκB activity and lowering their production of proinflammatory cytokines [83].”
Flagged first, then by citations
Cited by
Sorted by citations
Kalinkovich, A., & Livshits, G. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.008 · Cited by 882 · see citing works
The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis.
Crewe, C., An, Y. A., & Scherer, P. E. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88883 · Cited by 732 · see citing works
“The regulation of immune cell function and cytokine production in obese AT has been well studied (68), and it is now evident that the balance of pro- and antiinflammatory signals is critical for disease progression.”
Colonna, M. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00837-1 · Cited by 394 · see citing works
Tissue homeostasis and inflammation
Meizlish, M. L., Franklin, R. A., Zhou, X., & Medzhitov, R. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053734 · Cited by 364 · see citing works
Chemerin: a multifaceted adipokine involved in metabolic disorders
Helfer, G., & Wu, Q. (2018) · Journal of Endocrinology · doi:10.1530/joe-18-0174 · Cited by 317 · see citing works
Obesity accelerates T cell senescence in murine visceral adipose tissue
Shirakawa, K., Yan, X., Shinmura, K., Endo, J., Kataoka, M., Katsumata, Y., Yamamoto, T., Anzai, A., Isobe, S., Yoshida, N., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci88606 · Cited by 271 · see citing works
“Notably, the age-dependent development of SA–T cells, which may include autoreactive cells, is dependent on B cells (9).”
BackgroundHan, S., Zaretsky, A. G., Andrade‐Oliveira, V., Collins, N., Dzutsev, A. H., Shaik, J. S., da Fonseca, D. M., Harrison, O. J., Tamoutounour, S., Byrd, A. L., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.11.009 · Cited by 250 · see citing works
“This contrasts with what is currently understood in the context of inflammation, a setting associated with enhanced lipolysis of adipocytes (DiSpirito and Mathis, 2015; O’Neill et al., 2016).”
Pas de Deux: Control of Anti-tumor Immunity by Cancer-Associated Inflammation
Shalapour, S., & Karin, M. (2019) · Immunity · doi:10.1016/j.immuni.2019.06.021 · Cited by 229 · see citing works
“However, peripheral adipose depots also have a profound influence on adaptive immunity (DiSpirito and Mathis, 2015; Maurizi et al., 2018), increasing immune ageing and T cell exhaustion and dysfunction (Shalapour et al.”
BackgroundHigh-Resolution PET Imaging with Therapeutic Antibody-based PD-1/PD-L1 Checkpoint Tracers
Hettich, M., Braun, F., Bartholomä, M. D., Schirmbeck, R., & Niedermann, G. (2016) · Theranostics · doi:10.7150/thno.15253 · Cited by 194 · see citing works
“The noticeable PD-L1 expression detected in BAT contributes to the notion of BAT as an immunologically relevant tissue [40-42].”
BackgroundExercise-induced ’browning’ of adipose tissues
Aldiss, P., Betts, J., Sale, C., Pope, M., Budge, H., & Symonds, M. E. (2018) · Metabolism · doi:10.1016/j.metabol.2017.11.009 · Cited by 175 · see citing works
“Exercise training triggers multiple complex changes in immune function [84] and emerging evidence suggests that innate immune cells control brown and beige adipogenesis [85].”
BackgroundCaër, C., Rouault, C., Roy, T. L., Poitou, C., Aron‐Wisnewsky, J., Torcivia, A., Bichet, J.-C., Clément, K., Guerre-Millo, M., & André, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-02660-w · Cited by 157 · see citing works
Adipose Tissue: Physiology to Metabolic Dysfunction
Richard, A. J., White, U. A., Elks, C. M., & Stephens, J. M. (2020) · Europe PMC (PubMed Central) · Cited by 118 · see citing works
Adipose tissue in health and disease
Harvey, I. C., Boudreau, A., & Stephens, J. M. (2020) · Open Biology · doi:10.1098/rsob.200291 · Cited by 117 · see citing works
Liu, F., He, J., Wang, H., Zhu, D., & Bi, Y. (2020) · Obesity Surgery · doi:10.1007/s11695-020-04983-6 · Cited by 115 · see citing works
Ginaldi, L., & Martinis, M. D. (2016) · Current Medicinal Chemistry · doi:10.2174/0929867323666160907162546 · Cited by 109 · see citing works
“Conversely, in lean humans adipose tissue macrophages may promote tissue remodeling and temper inflammation by secreting anti-inflammatory cytokines [88].”
BackgroundMetabolic Reprogramming and Longevity of Tissue-Resident Memory T Cells
Pan, Y., & Kupper, T. S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01347 · Cited by 100 · see citing works
LaMarche, N. M., Kane, H., Kohlgruber, A. C., Dong, H., Lynch, L., & Brenner, M. B. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.05.017 · Cited by 92 · see citing works
Margina, D. M., Ungurianu, A., Purdel, C. N., Nițulescu, G. M., Tsoukalas, D., Sarandi, E., Thanasoula, M., Burykina, T. I., Tekos, F., Djordjević, A. B., et al. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111558 · Cited by 86 · see citing works
T Cell Immunosenescence in Aging, Obesity, and Cardiovascular Disease
Shirakawa, K., & Sano, M. (2021) · Cells · doi:10.3390/cells10092435 · Cited by 87 · see citing works
“Obesity-associated VAT inflammation involves a complex network of immune cells, including types involved in the acquired immune response (multiple subsets of T cells and B cells), innate immune cells such as macrophages [23,24,58], and chronic low-grade inflammation in VAT linked to the development of obesity-associat…”
BackgroundAn intracrine view of sex steroids, immunity, and metabolic regulation
Rubinow, K. B. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.03.001 · Cited by 82 · see citing works
“Notably, immune cell populations in metabolic tissues contribute to the regulation of insulin sensitivity and energy metabolism in neighboring cells through the secretion of paracrine mediators [43,44].”
BackgroundAngiopoietin-2 in white adipose tissue improves metabolic homeostasis through enhanced angiogenesis
An, Y., Sun, K., Joffin, N., Zhang, F., Deng, Y., Donzé, O., Kusminski, C. M., & Scherer, P. E. (2017) · eLife · doi:10.7554/elife.24071 · Cited by 77 · see citing works
“Obesity is frequently associated with inflammation, and chronic unresolved AT inflammation is observed under obese conditions and tightly connected with AT angiogenesis (DiSpirito and Mathis, 2015; Lee, 2005).”
BackgroundRuscica, M., Baragetti, A., Catapano, A. L., & Norata, G. D. (2016) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2016.12.005 · Cited by 67 · see citing works
Adipose tissue at the nexus of systemic and cellular immunometabolism
Kohlgruber, A. C., LaMarche, N. M., & Lynch, L. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.09.005 · Cited by 60 · see citing works
Adipose‐tissue regulatory T cells: Critical players in adipose‐immune crosstalk
Becker, M., Levings, M. K., & Daniel, C. (2017) · European Journal of Immunology · doi:10.1002/eji.201646739 · Cited by 58 · see citing works
The Role of Adipocytes in Tissue Regeneration and Stem Cell Niches
Shook, B. A., Rivera-Gonzalez, G. C., Ebmeier, S., Grisotti, G., Zwick, R. K., & Horsley, V. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125426 · Cited by 58 · see citing works
“These ATMs are similar to inflammatory macrophages described in other tissues (DiSpirito & Mathis 2015, Lumeng et al. 2007, Nguyen et al. 2007).”
BackgroundSite-Specific Immuno-PET Tracer to Image PD-L1
Wissler, H. L., Ehlerding, E. B., Lyu, Z., Zhao, Y., Zhang, S., Eshraghi, A. R., Buuh, Z. Y., McGuth, J. C., Guan, Y., Engle, J. W., et al. (2019) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.9b00010 · Cited by 55 · see citing works
Circadian Rhythms in Adipose Tissue Physiology
Kiehn, J., Tsang, A. H. K., Heyde, I., Leinweber, B., Kolbe, I., Leliavski, A., & Oster, H. (2017) · Comprehensive physiology · doi:10.1002/cphy.c160017 · Cited by 60 · see citing works
Subcutaneous adipose tissue biology in metabolic syndrome
Jialal, I., & Devaraj, S. (2018) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2017-0074 · Cited by 53 · see citing works
“There is a serious paucity of data on other immune cells such as eosinophils, mast cells, neutrophils and different subtypes of lymphocytes in the AT [36].”
BackgroundTransgenic overexpression of VEGF-C induces weight gain and insulin resistance in mice
Karaman, S., Hollmén, M., Yoon, S., Alkan, H. F., Alitalo, K. K., Wolfrum, C., & Detmar, M. J. (2016) · Scientific Reports · doi:10.1038/srep31566 · Cited by 50 · see citing works
“Since (1) serum levels of endogenous (mouse) VEGF-C have been reported to be around 50–100 pg/mL14, (2) mouse and human VEGF-C have similar receptor binding affinities, (3) the lowest detectable amount of hVEGF-C in serum is lower than endogenous VEGF-C levels, and (4) the hVEGF-C levels detected in SWAT are 50 fold h…”
BackgroundAntwi, S. O., Mousa, O. Y. S., & Patel, T. C. (2018) · Annals of Hepatology · doi:10.5604/01.3001.0010.8659 · Cited by 50 · see citing works
Brykczynska, U., Geigges, M., Wiedemann, S. J., Dror, E., Böni‐Schnetzler, M., Hess, C., Donath, M. Y., & Paro, R. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.005 · Cited by 48 · see citing works
“Indeed, in both islet and peritoneal macrophages, we did not observe upregulation of Il1b, although it is an established hallmark of inflammation in ATMs in HFD-fed mice and obese humans (Bing, 2015; DiSpirito and Mathis, 2015).”
BackgroundInfluentialGilleron, J., Bouget, G., Ivanov, S., Méziat, C., Ceppo, F., Vergoni, B., Djedaini, M., Soprani, A., Dumas, K., Jacquel, A., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.083 · Cited by 46 · see citing works
Lechner, J., Rudi, T., & von Baehr, V. (2018) · Clinical Cosmetic and Investigational Dentistry · doi:10.2147/ccide.s184498 · Cited by 45 · see citing works
Exercise and Adipose Tissue Immunity: Outrunning Inflammation
Winn, N. C., Cottam, M. A., Wasserman, D. H., & Hasty, A. H. (2021) · Obesity · doi:10.1002/oby.23147 · Cited by 43 · see citing works
“discussions on the topic have been published (1,19).”
BackgroundClinical Significance of Serum Adiponectin and Resistin Levels in Liver Cirrhosis
Silva, T. E., Silva, M. C., Corrêa, C. G., Denardin, G., Alencar, M. L. A., Coelho, M. S. P. H., Wildner, L. M., Bazzo, M. L., González‐Chica, D. A., Dantas-Corrêa, E. B., et al. (2018) · Annals of Hepatology · doi:10.5604/01.3001.0010.8660 · Cited by 41 · 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
“…processes, including adipocyte hypertrophy, hypoxia, and immune cell infiltration, are closely linked to adipocyte dysfunction, resulting in insulin resistance and metabolic complications (Ham et al. 2013; Choe et al. 2014; Rosen and Spiegelman 2014; DiSpirito and Mathis 2015; Sohn et al. 2018).”
BackgroundCouturier, J. P., Agarwal, N., Nehete, P. N., Baze, W. B., Barry, M. A., Sastry, K. J., Balasubramanyam, A., & Lewis, D. E. (2016) · Retrovirology · doi:10.1186/s12977-016-0260-2 · Cited by 39 · see citing works
“well-known that a range of immune cells reside in or migrate into adipose tissues and affect their metabolic signals [6, 7], but adipocytes and other adipose tissueresident cells interact with CD4 T cells and macrophages which has important implications for HIV pathogenesis.”
Immune Cells Gate White Adipose Tissue Expansion
Cox, A. R., Chernis, N., Masschelin, P. M., & Hartig, S. M. (2019) · Endocrinology · doi:10.1210/en.2019-00266 · Cited by 39 · see citing works
Rombaldová, M., Janovská, P., Kopecký, J., & Kuda, O. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.06.170 · Cited by 32 · see citing works
Fatty acid binding protein 4/aP2-dependent BLT1R expression and signaling
Hertzel, A. V., Xu, H., Downey, M. C., Kvalheim, N., & Bernlohr, D. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m074542 · Cited by 26 · see citing works
Mesenchymal stromal cells as conductors of adipose tissue remodelingPreprint
Cannavino, J., & Gupta, R. K. (2023) · Genes & Development · doi:10.1101/gad.351069.123 · Cited by 24 · see citing works
Visceral adipose tissue mesenchymal stromal cells in the intersection of immunology and metabolism
Spallanzani, R. G. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00341.2020 · Cited by 24 · see citing works
Modulation of T Cell Activation in Obesity
Morin, S. O., Poggi, M., Alessi, M., Landrier, J., & Nunès, J. A. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6746 · Cited by 24 · see citing works
“These food-derived antigens via these triglyceride carriers could be cleared in the AT to stimulate pro-inflammatory T cells (24, 28, 83).”
Adipose depot gene expression and intelectin‐1 in the metabolic response to cancer and cachexia
Miller, J. D., Dreczkowski, G., Ramage, M. I., Wigmore, S. J., Gallagher, I. J., & Skipworth, R. J. E. (2020) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12568 · Cited by 23 · see citing works
Li, Y.-H., Wen, K., Zhu, L., Lv, S.-K., Cao, Q. N., Li, Q., Deng, L., Chen, T., Wang, X., Deng, K., et al. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00134 · Cited by 21 · see citing works
“All these cytokines and adipokines seriously affected the differentiation and functions of adipocytes through interfering with insulin signaling and intracellular stress pathways (11, 12).”
BackgroundThe role of innate immunity in the regulation of brown and beige adipogenesis
Alexaki, V. I., & Chavakis, T. (2016) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-016-9342-7 · Cited by 21 · see citing works
“So far, eosinophils, M2 macrophages and type 2 innate lymphoid cells (ILC2) have been identified to reside in the lean WAT and to regulate beige adipogenesis (reviewed in [68,74]).”
BackgroundHan, S. M., Park, E. S., Park, J., Nahmgoong, H., Choi, Y. H., Oh, J., Yim, K. M., Lee, W. T., Lee, Y. K., Jeon, Y. G., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-44181-3 · Cited by 19 · see citing works
“Immune cells in adipose tissue are important regulators of adipose tissue metabolism 12 .”
BackgroundLiu, X., Perakakis, N., Gong, H., Chamberland, J. P., Brinkoetter, M. T., Hamnvik, O. R., & Mantzoros, C. S. (2016) · Metabolism · doi:10.1016/j.metabol.2016.09.003 · Cited by 19 · see citing works
“g IFN-γ) in visceral adipose tissue, are activated either by macrophages or directly by adipocytes in obesity, joining CD8+T cells as crucial effector lymphocytes (7, 8).”
BackgroundLIGHT/TNFSF14 signaling attenuates beige fat biogenesis
Kou, Y., Liu, Q., Liu, W., Sun, H., Liang, M., Kong, F., Zhang, B., Wei, Y., Liu, Z., & Wang, Y. (2018) · The FASEB Journal · doi:10.1096/fj.201800792r · Cited by 18 · see citing works
“These immune cells tend to cross-talk with adipocytes and contribute to the regulation ofmetabolic homeostasis (6, 7).”
BackgroundNovel antiadipogenic effect of menadione in 3T3-L1 cells
Funk, M. I., Conde, M. A., Piwien‐Pilipuk, G., & Uranga, R. M. (2021) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2021.109491 · Cited by 18 · see citing works
Adipose Tissue in Health and Disease
Leff, T., & Granneman, J. G. (2010) · Wiley eBooks · doi:10.1002/9783527629527 · Cited by 18 · see citing works
Zhou, Q., Fu, Y., Liang-an, H., Li, Q., Jin, M., & Jiang, E. (2017) · Journal of Asthma · doi:10.1080/02770903.2017.1355378 · Cited by 16 · see citing works
“To understand these factors, hundreds of adipokineswere divided into subgroups that have pro- or anti-inflammatory activities [5].”
BackgroundFigueroa‐Vega, N., Marín-Aragón, C. I., López-Aguilar, I., Ibarra‐Reynoso, L. D. R., Pérez-Luque, E. L., & Malacara, J. M. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228637 · Cited by 15 · see citing works
“perturbations of immune system and dysregulated adipose tissue (AT) homeostasis [30].”
BackgroundSeasonal variations of adipose tissue in Tupaia belangeri (Mammalia: Scandentia: Tupaiidae)
Li, M., Hao, Z., Wanlong, Z., & Zhengkun, W. (2019) · The European Zoological Journal · doi:10.1080/24750263.2019.1572798 · Cited by 12 · see citing works
“…molecules produced by immune cells in WAT and BAT and their regulation of the development and proliferation of beige and brown adipocytes (Brestoff & Artis 2015; DiSpirito & Mathis 2015), and activation of beige adipocytes in vitro, have become current research directions (Steinbring et al. 2017).”
BackgroundKuchler, J. C., Siqueira, B. S., Ceglarek, V. M., Chasko, F. V., Moura, I. C., Sczepanhak, B. F., Vettorazzi, J. F., Balbo, S. L., & Grassiolli, S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.672027 · Cited by 11 · see citing works
Circulating sex steroids coregulate adipose tissue immune cell populations in healthy men
Rubinow, K. B., Chao, J. H., Hagman, D. K., Kratz, M., Yserloo, B. V., Gaikwad, N. W., Amory, J. K., & Page, S. T. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00075.2017 · Cited by 11 · see citing works
“Thus through the secretion of paracrine effectors including growth and angiogenic factors, matrix metalloproteinases, and cytokines, these tissue immune cells are critical mediators of lipid and glucose metabolism, adipocyte differentiation, and tissue remodeling (23, 47, 52, 54, 55, 75, 76, 86, 88).”
BackgroundHow Adipocytes Orchestrate Inflammation Within Adipose Tissue?
Higos, R., Renzi, G., Taillandier, P., Merabtene, F., Rouault, C., Abatan, J. B., Lambert, M., Dugail, I., Clément, K., Marcelin, G., et al. (2025) · Biomolecules · doi:10.3390/biom16010059 · Cited by 10 · see citing works
“IL-33 has emerged as a pivotal mediator in these niches, particularly in regulating anti-inflammatory Tregs and ILC2s [197].”
Adipoz doku ve adipoz dokudan salgılanan bazı proteinler
DEMİRCİ, Ş., & Gün, C. (2017) · Mehmet Akif Ersoy Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi · doi:10.24998/maeusabed.338105 · Cited by 9 · see citing works
Adorni, C. S., Corrêa, C. R., Vileigas, D. F., de Campos, D. H. S., Padovani, C. R., Minatel, I. O., & Cicogna, A. C. (2017) · Nutrire · doi:10.1186/s41110-017-0042-1 · Cited by 8 · see citing works
“All changes, metabolic/hormonal/inflammatory, viewed in obese rats probably result from adipose tissue dysfunction; this imbalance in adipose tissue is characterized by adipocyte hypertrophy followed by reduced capacity of triglyceride storage and increased production of inflammatory adipokines, oxidative stress, and…”
BackgroundGhosh, A. R., Bandopadhyay, P., Sarkar, J., Khanna, S., Chaudhuri, T., Tantia, O., Chakrabarti, P., & Ganguly, D. (2023) · Obesity · doi:10.1002/oby.23805 · Cited by 7 · see citing works
Integrated control of leukocyte compartments as a feature of adaptive physiology
Jaschke, N., & Wang, A. (2025) · Immunity · doi:10.1016/j.immuni.2025.01.013 · Cited by 7 · see citing works
Circadian Rhythms in Adipose Tissue Physiology
Kiehn, J., Tsang, A. H. K., Heyde, I., Leinweber, B., Kolbe, I., Leliavski, A., & Oster, H. (2017) · Comprehensive physiology · doi:10.1002/j.2040-4603.2017.tb00751.x · Cited by 6 · see citing works
“Macrophages are the best-studied immune cells in metabolic inflammation (145, 367, 391, 431, 440), though the underlying cause and functions of ATMs in obesity remain poorly understood.”
Isolation of Immune Cells from Adipose Tissue for Flow Cytometry
Brestoff, J. R. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6820-6_6 · Cited by 5 · see citing works
Kim, H. J., Kim, Y. J., & Seong, J. K. (2025) · The Journal of Physiology · doi:10.1113/jp285975 · Cited by 4 · see citing works
Bikis, C., Tzanavari, T., Alexandraki, K., & Theocharis, S. E. (2018) · Hormones and Cancer · doi:10.1007/s12672-018-0327-8 · Cited by 4 · see citing works
Instruction of Immunometabolism by Adipose Tissue: Implications for Cancer Progression
Raja, R., Wu, C. W., Limbeck, F., Butler, K. A., Acharya, A. P., & Curtis, M. (2021) · Cancers · doi:10.3390/cancers13133327 · Cited by 4 · see citing works
“Adipose tissue can be broadly grouped into three main types—white, brown, and beige, which have different anatomic distributions and homeostatic functions [3].”
BackgroundLiquid biopsy for microbiome profiling through nucleotide analysis
Kolodkin‐Gal, I., & Frenkel‐Morgenstern, M. (2025) · Trends in biotechnology · doi:10.1016/j.tibtech.2025.05.021 · Cited by 3 · see citing works
Serendipitous Discovery of T Cell–Produced KLK1b22 as a Regulator of Systemic Metabolism
Arwood, M. L., Sun, I., Patel, C. H., Sun, I.-M., Oh, M. H., Bettencourt, I. A., Claiborne, M. D., Chan‐Li, Y., Zhao, L., Waickman, A. T., et al. (2023) · ImmunoHorizons · doi:10.4049/immunohorizons.2300016 · Cited by 3 · see citing works
“Adipose tissue is a crucial organ for the maintenance of glucose homeostasis, and the immune system undertakes a fundamental role in its regulation (37, 42).”
InfluentialRelationship Between Visceral Fat Tissue and Exercise
Ceviz, E. (2024) · Türk Spor Bilimleri Dergisi · doi:10.46385/tsbd.1448060 · Cited by 3 · see citing works
Obesity, inflammation, and diseases of the gastrointestinal tract
Tillman, A. C., & Giorgi, M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90960-0.00008-4 · Cited by 2 · see citing works
Siwiec, J., Kuźnik‐Trocha, K., Winsz‐Szczotka, K., Komosińska‐Vassev, K., Siwiec, A., & Olczyk, K. (2025) · Pharmaceuticals · doi:10.3390/ph18091423 · Cited by 1 · see citing works
“However, given their ability to modulate immune and inflammatory responses, their involvement in the development of juvenile idiopathic arthritis appears undeniable [11–14].”
Rammah, M., Romero, A. R., Halabi, N. M., Abuaqel, S. W. J., Guennoun, A., Dömling, P. D. A., Shan, J., & Chouchane, L. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-07970-0 · Cited by 1 · see citing works
“Chronic low-grade inflammation in WAT is a central pathological feature of obesity, and a key driver of insulin resistance, type 2 diabetes, and cardiovascular disease [10].”
Land, W. G. (2018) · Springer eBooks · doi:10.1007/978-3-319-78655-1_9 · Cited by 1 · see citing works
“Of note, the continuous extensive expansion of adipose tissue during obesity steadily increases its ability to act as an immunological tissue that can switch from controlled to uncontrolled systemic inflammation associated with considerable pathologies [153] [154] [155] .”
Background"The Place of Osteoimmunology in the Pathogenesis of Rheumatic Joint and Bone Diseases"
Momcheva, I. I. (2023) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2023.50.007894
Reaktywność układu odpornościowego w niektórych zaburzeniach psychicznych
Kozłowska, E., Żelechowska, P., Sobów, T., & Brzezińska‐Błaszczyk, E. (2015) · DOAJ (DOAJ: Directory of Open Access Journals) · doi:10.15557/pipk.2015.0027
Is Microbiota Making You Fat? From Microbiota and Immune System to Obesity and Disease
Tuna, M. A., & Salazar, J. R. (2017) · Current Tropical Medicine Reports · doi:10.1007/s40475-017-0112-8
Sabour, H. (2019) · Springer eBooks · doi:10.1007/978-3-030-16073-9_18
Denton, N. (2021) · Oxford University Press eBooks · doi:10.1093/med/9780198865278.003.0003
Ilich, J. Z., Kelly, O. J., Gilman, J. C., Cvijetić, S., & Boschiero, D. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-820088-9.00014-7
It takes a village to skew a lymph node
Thornton, E. E., & Arnon, T. I. (2022) · Immunity · doi:10.1016/j.immuni.2022.09.008
den Braanker, H., van der Valk, E. S., & Bisoendial, R. J. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14217641
“Rather than a homogeneous lipid depot, adipose tissue comprises a complex network of specialized cell types working in concert to maintain metabolic homeostasis, regulate immune function, and coordinate systemic energy balance [63].”
Expression and clinical significance of fatty acid metabolism–related genes in PBMCs of SSc patients
Wang, Y., Yu, X., Lei, T., Li, X., Zhong, L., Wang, S., Zhang, Q., & Qing, Y. (2026) · Clinical Rheumatology · doi:10.1007/s10067-025-07881-3
“The interaction between adipocytes and immune cells can result in metabolic dysfunction [10].”
Gai, Y., Ma, G., He, R. R., Gu, Z., Wang, M., Mao, S., & Chen, Y. (2026) · Journal of Animal Science · doi:10.1093/jas/skag058
“Beyond thermoregulation, sWAT also serves as a pro-and anti-inflammatory regulator (DiSpirito and Mathis 2015).”
Inflammation du tissu adipeux au cours de l'obésité humaine : implication des lymphocytes Th17
Caër, C. (2016) · theses.fr (ABES) · doi:10.70675/65eca5dczaa63z4e9az82dbzb223bfe8ef82 · Cited by 1 · see citing works
CD28 : nouvelles données sur un récepteur majeur de la costimulation lymphocytaire T
Morin, S. O. (2017) · theses.fr (ABES) · doi:10.70675/cb01635fz2f63z43e2zad0cz210485c4c5cf
The thermogenic roles of bioactive compounds: A comprehensive bibliometric review
Günalan, E., Turgut, R., & Günalan, E. (2026) · Studies in natural products chemistry · doi:10.1016/b978-0-443-49148-1.00013-5
- Authors
- DiSpirito, J. R., & Mathis, D.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Seminars in Immunology
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 27
- Issue
- 5
- Pages
- 315-321
- ISSN
- 1044-5323 (ISSN-L)
- PMC
- PMC4681639
- OpenAlex
- W2175576992
- Cited by
- 88
- References
- 94
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 8 · 2020: 10 · 2019: 6 · 2018: 11 · 2017: 17 · 2016: 13 · 2015: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (RO1DK092541)
- American Diabetes Association ADA (1-16-PDF-028)
- 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
- adipose tissue homeostasis, adipocytes, white adipocytes, brown adipocytes, beige adipocytes, adipokines, low-grade inflammation, obesity, metabolic dysfunction, insulin resistance, innate immunity, adaptive immunity, diet composition, gut microbiota, adipose tissue inflammation
- MeSH terms
- Gastrointestinal Microbiome, Adipose Tissue, Animals, Cell Communication, Diet, Elasticity, Energy Metabolism, Homeostasis, Humans, Immune System, Immunity, Inflammation, Obesity, Signal Transduction, Adipocytes
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
