The DOI matches its Crossref record; 102 of the 102 references it cites were found in a registry or an index.
Obesity is associated with macrophage accumulation in adipose tissue
Open accessAbstract
Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications.To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (A y ) and obese (Lep ob ).We found that the expression of 1,304 transcripts correlated significantly with body mass.Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass.Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80 + ) was significantly and positively correlated with both adipocyte size and body mass.Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68.Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1 op/op ) mice suggest that these F4/80 + cells are CSF-1 dependent, bone marrow-derived adipose tissue macrophages.Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-α expression and significant amounts of iNOS and IL-6 expression.Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.
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“Aging is also associated with macrophage infiltration into primarily visceral adipose depots which drives a pro-inflammatory state and further increases adipose dysfunction (40).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [40]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As metabolic syndrome is associated with significant macrophage accumulation in adipose tissue,69”
From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [69]
Experimental — accuracy not yet measuredIn the citing paper
“Activated monocytes that give rise to M1 and M2 macrophages produce even more inflammatory compounds that probably appear in the circulation57.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [57]
In the citing paper
“In adipose tissue from lean subjects, approximately 10% of cells stained positive for macrophages, but in obese subjects, this number increased to up to 50% [38].”
From Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences (2020) · cites this paper as [38]
In the citing paper
“In fact, more than 40% of the total adipose tissue cell content from obese rodents and humans was comprised of macrophages compared with approximately 10% in lean counterparts (101).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [101]
In the citing paper
“In addition, macrophages were responsible for the majority of Tnfa expression in adipose tissue and contributed significantly to Il6 and Ikbkb expression (101, 102).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [101]
In the citing paper
“In 2003, the novel discovery that adipose tissue from obese mice and humans is infiltrated with macrophages provided a major mechanistic advance into understanding how obesity propagates inflammation (101, 102).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [101]
In the citing paper
“Moreover, this intermuscular adipose depot is infiltrated with approximately 3 times more macrophages in skeletal muscle from obese compared with lean mice (101).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [101]
In the citing paper
“These include increased production of inflammatory cytokines, 35,36 plasminogen activator inhibitor-1, 37 and other bioactive products 38 -40 ; at the same time the potentially protective adipokine, adiponectin, is reduced.41,42”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [36]
In the citing paper
“Macrophages comprise the largest population of resident immune cells in visceral AT, constituting up to 10% of AT cells in mice (10).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [10]
In the citing paper
“Weisberg et al. demonstrated that subcutaneous AT macrophage infiltration was increased in obese patients, similar to that observed in obese mice (10).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [10]
In the citing paper
“Several detailed studies have also reported a higher macrophage count in visceral AT of insulin-resistant obese patients compared with lean or insulin-sensitive obese counterparts, an effect that was significantly mitigated following bariatric surgery (10,(114)(115)(116).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [10]
In the citing paper
“Several detailed studies have also reported a higher macrophage count in visceral AT of insulin-resistant obese patients compared with lean or insulin-sensitive obese counterparts, an effect that was significantly mitigated following bariatric surgery (10,(114)(115)(116).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [10]
In the citing paper
“The combination of microhypoxia and lipid overload triggers the recruitment of immune cells, such as macrophages in the adipose tissue and their activation ([103](#B103), [129](#B129), [171](#B171)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [171]
In the citing paper
“In 2003, two independent articles in the JCI highlighted the infiltration of macrophages into expanding AT as an important physiological phenomenon (5,6).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [6]
In the citing paper
“Excess body adiposity has been associated with activation of macrophages and associated inflammation in a variety of peripheral tissues including WAT, liver, skeletal muscle and the vasculature and eventually is accompanied by increased circulating plasma levels of pro-inflammatory cytokines (193, 207).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [193]
In the citing paper
“Visceral adipose tissue has an increased number of adipose resident macrophages.”
From The Vasculature in Prediabetes (2018) · cites this paper as [81]
In the citing paper
“Increased recruitment of pro-inflammatory macrophages to muscle167 and adipose81 results in transforming growth factor β (TGFβ)-mediated fibrosis.168”
From The Vasculature in Prediabetes (2018) · cites this paper as [81]
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- 10.1210/jc.82.5.1313 · DOI · Paper page
- 10.1210/en.136.5.2143 · DOI
- Torres, 1999, Invest. Ophthalmol. Vis. Sci., 40, 3194
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Grundy, S. M., Cleeman, J. I., Daniels, S. R., Donato, K. A., Eckel, R. H., Franklin, B. A., Gordon, D. J., Krauss, R. M., Savage, P. J., Smith, S. C., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.169404 · Cited by 11,961
Inflammation and metabolic disorders
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Metadata
- Authors
- Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W.
- Affiliations
- Columbia University Irving Medical Center (US)
- Columbia University (US)
- Corresponding author
- Ferrante, Anthony W.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-12-15
- Volume
- 112
- Issue
- 12
- Pages
- 1796-1808
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC296995
- OpenAlex
- W2008869160
- Cited by
- 10,041
- References
- 99
- Citations by year
- 2026: 265 · 2025: 337 · 2024: 420 · 2023: 373 · 2022: 460 · 2021: 504 · 2020: 524 · 2019: 494 · 2018: 536 · 2017: 537 · 2016: 530 · 2015: 558 · 2014: 575 · 2013: 683 · 2012: 554
- FWCI
- 130.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Journal of Clinical Investigation (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Russell Berrie Foundation
- National Institutes of Health (K08 DK)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064773, R01DK052431, K08DK059960, R01DK066525)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- obesity, adipose tissue macrophages, macrophage accumulation, perigonadal adipose tissue, F4/80, CD68, bone marrow-derived macrophages, adipose tissue inflammation, TNF-α, inducible nitric oxide synthase, interleukin-6, adipocyte size, body mass, subcutaneous adipose tissue
- MeSH terms
- CD68 Molecule, Adipose Tissue, Animals, Body Weight, Cell Separation, Female, Flow Cytometry, Humans, Immunohistochemistry, Liver, Macrophages, Male, Mice, Inbred C57BL, Obesity, RNA, Messenger, Time Factors, Tumor Necrosis Factor-alpha, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Interleukin-6, Immunophenotyping, Leukocyte Common Antigens, Nitric Oxide Synthase, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Mice, Nitric Oxide Synthase Type II
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