Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice
Open accessAbstract
Obesity is accompanied by adipocyte death and accumulation of macrophages and mast cells in expanding adipose tissues. Considering the differences in biological behavior of fat found in different anatomical locations, we explored the distribution of mast cells, solitary macrophages, and crown-like structures (CLS), the surrogates for dead adipocytes, in subcutaneous and abdominal visceral fat of lean and diet-induced obese C57BL/6 mice. In fat depots of lean mice, mast cells were far less prevalent than solitary macrophages. Subcutaneous fat contained more mast cells, but fewer solitary macrophages and CLS, than visceral fat. Whereas no significant change in mast cell density of subcutaneous fat was observed, obesity was accompanied by a substantial increase in mast cells in visceral fat. CLS became prevalent in visceral fat of obese mice, and the distribution paralleled mast cells. Adipose tissue mast cells contained and released preformed TNF-α, the cytokine implicated in the pathogenesis of obesity-linked insulin resistance. In summary, subcutaneous fat differed from visceral fat by immune cell composition and a lower prevalence of CLS both in lean and obese mice. The increase in mast cells in visceral fat of obese mice suggests their role in the pathogenesis of obesity and insulin resistance.
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Our data confirm a more pronounced accumulation of large Cd68-eGFP+ clusters in the visceral fat compared with in the subcutaneous fat.
“Consistent with previous reports, our data confirm a more pronounced accumulation of large Cd68-eGFP+ clusters in the visceral fat compared with in the subcutaneous fat38.”
From A deep-learning framework reveals whole-body perturbations at cell level (2026) · cites this paper as [38]
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“In obesity, adipocytes release an array of proinflammatory cytokines and chemokines, including tumor necrosis factor– (TNF), interleukin 6 (IL-6), and C-C motif chemokine ligand 2 (CCL2), leading to increased recruitment of proinflammatory immune cells, including macrophages (5–7), T helper 1 (TH1) or TH17 lymphocyt…”
From neutrophils to macrophages: Differences in regional adipose tissue depots
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“It is well-known that saturated GAT accumulates CLS 20,25 , a phenomenon also observed in our study.”
InfluentialInterleukin-1 beta: a potential link between stress and the development of visceral obesity
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“Based upon their anatomical location, WAT depots are heterogeneous in their innervation pattern [75-77], composition [78-81] and function [81-83].”
BackgroundInfluentialAltintas, M. M., Rossetti, M. A., Nayer, B., Puig, A., Zagallo, P., Ortega, L. M., Johnson, K. B., McNamara, G. T., Reiser, J., Mendez, A. J., et al. (2011) · Lipids in Health and Disease · doi:10.1186/1476-511x-10-198 · Cited by 55 · see citing works
“There is also a remarkable heterogeneity in the severity of adipose tissue inflammation in different visceral fat depots in obese subjects [3,12].”
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“types of white AT is the lower number of CLS present in subcutaneous AT compared with visceral AT both in obese and lean mice [55].”
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“WAT is capable of expressing stress-responsive DAMPS such as heat shock protein (Hsp)-72 and inflammatory proteins such as MCP-1, tumor necrosis factor alpha (TNF-a), interleukin (IL)-1b, IL-6, IL-10 (Altintas et al., 2011; Batra and Siegmund, 2012; Caspar-Bauguil et al., 2009).”
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“1% aqueous toluidine blue (Sigma‐Aldrich; Merck KGaA, Darmstadt, Germany) at room temperature, the histological images were used to quantify the number of mast cells present, as previously described (15).”
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“macrophages that infiltrate adipose assemble around very small (dying/injured) adipocytes in CLSs (13,16).”
BackgroundInfluentialZinc and Zinc Transporters in Dermatology
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“Mast cells are linked to allergic reactions, and they accumulate in large numbers in the papillary dermis and are also found in the subcutaneous fat [38].”
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“They also appear to be increased in animal models of obesity and in limited studies in patients with obesity and diabetes (3, 7, 25, 28), implicating a potential role in metabolic dysregulation.”
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“The expression profile of pro-inflammatory cytokines in response to Sfrp1 loss and the HFD was not always consistant between the gonadal fat pad and the mammary gland which was expected considering that the immune responses differ in visceral and subcutaneos fat pads [63].”
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“reported that macrophage infiltration into EAT was the most severe event in visceral adipose tissues [30].”
BackgroundInfluentialRetractedNo Role for Mast Cells in Obesity-Related Metabolic Dysregulation
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“and CD8 effector T cells), B cells, and mast cells (2, 4, 5).”
Background[Cells of innate and adaptive immunity in type 2 diabetes and obesity].
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Multinucleated Giant Cells in Adipose Tissue Are Specialized in Adipocyte Degradation
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“Although susceptibility of AT depots to obesity-induced adipocyte death is different, adipocyte death is increased by 10- to 100-fold as a result of obesity (24).”
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“Epididymal fat is a representative visceral fat widely used in metabolic studies using mouse models [21].”
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Obesity, Inflammation, and Insulin Resistance
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“These results could be attributed to several factors, including (a) greater chronic inflammation in adolescents with obesity as evidenced by higher levels of IL-6 [17]; (b) greater visceral adipose tissue mass, which has 4-fold more crown-like structures [18] that participate in the expression of IL-6 and in the expre…”
BackgroundAltintas, M. M., Nayer, B., Walford, E. C., Johnson, K. B., Gaidosh, G., Reiser, J., Cruz-Munoz, N. F. D. L., Ortega, L. M., & Nayer, A. (2012) · Lipids in Health and Disease · doi:10.1186/1476-511x-11-21 · Cited by 29 · see citing works
“We also showed that dietinduced obesity in mice is associated with a marked increase in mast cells in the visceral, but not in the subcutaneous, fat depots [11].”
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“This finding is consistent with results from studies demonstrating that obesity is associated with more pronounced infiltration of macrophages in visceral compared to subcutaneous adipose tissue [21].”
Dietary cholesterol is essential to mast cell activation and associated obesity and diabetes in mice
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Sphingosine 1-Phosphate Regulates Obesity and Glucose Homeostasis
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“In obese humans and mice, macrophages accumulate more in VAT than in SAT [37,38,53].”
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“The average of these four sections was taken as the number of CLS/field (Altintas et al. 2011).”
BackgroundImmune cells and metabolic dysfunction
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“Counts of mast cells in lean adipose tissue are relatively low, but increase with fat accumulation in humans as well as in animal models [36, 37], which suggest a contribution to diet-induced obesity and insulin resistance.”
Mouse model of the adipose organ: the heterogeneous anatomical characteristics
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Immunometabolism in Obese Asthmatics: Are We There Yet?
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“Increased visceral fat mast cells, neutrophil, and macrophage infiltration has been shown to be associated with insulin resistance in rodents (Altintas et al., 2011; Elgazar-Carmon et al., 2008).”
BackgroundImmune and Inflammatory Signaling Pathways in Exercise and Obesity
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A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice
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“S1 N ), in line with their proposed role in adipose tissue remodeling (18–20).”
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“percentage of total adipocytes in each image (29).”
BackgroundMast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice.
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Obesity reduces methionine sulphoxide reductase activity in visceral adipose tissue
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“Crown-like structures (CLS), which consist of macrophages surrounding dead adipocytes [2, 7, 31], were also found only in visceral adipose tissue (Fig.”
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Contribution of Adipose Tissue to Development of Cancer
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“A similar study published the same year by the same group also found dramatically increased mast cell infiltration in mesenteric and perirenal adipose, but no significant obesity-induced changes in mast cell density in inguinal subcutaneous adipose (9).”
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- Authors
- Altintas, M. M., Azad, A., Nayer, B., Contreras, G., Zaias, J., Faul, C., Reiser, J., & Nayer, A.
- Affiliations
- University of Miami (US)
- Corresponding author
- Nayer, Ali
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 52
- Issue
- 3
- Pages
- 480-488
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC3035684
- OpenAlex
- W2089000416
- Cited by
- 198
- References
- 48
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 14 · 2023: 6 · 2022: 14 · 2021: 10 · 2020: 17 · 2019: 12 · 2018: 14 · 2017: 19 · 2016: 12 · 2015: 19 · 2014: 13 · 2013: 21 · 2012: 9
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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
- mast cells, macrophages, crown-like structures, subcutaneous adipose tissue, visceral fat, obesity, adipocyte death, TNF-α, insulin resistance, adipose tissue inflammation, diet-induced obesity, C57BL/6 mice
- MeSH terms
- Animals, Diet, Epididymis, Macrophages, Male, Mast Cells, Mice, Inbred C57BL, Obesity, Thinness, Subcutaneous Fat, Intra-Abdominal Fat, Mice
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