Reduction of Macrophage Infiltration and Chemoattractant Gene Expression Changes in White Adipose Tissue of Morbidly Obese Subjects After Surgery-Induced Weight Loss
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In human obesity, the stroma vascular fraction (SVF) of white adipose tissue (WAT) is enriched in macrophages. These cells may contribute to low-grade inflammation and to its metabolic complications. Little is known about the effect of weight loss on macrophages and genes involved in macrophage attraction. We examined subcutaneous WAT (scWAT) of 7 lean and 17 morbidly obese subjects before and 3 months after bypass surgery. Immunomorphological changes of the number of scWAT-infiltrating macrophages were evaluated, along with concomitant changes in expression of SVF-overexpressed genes. The number of scWAT-infiltrating macrophages before surgery was higher in obese than in lean subjects (HAM56+/CD68+; 22.6 ± 4.3 vs. 1.4 ± 0.6%, P < 0.001). Typical “crowns” of macrophages were observed around adipocytes. Drastic weight loss resulted in a significant decrease in macrophage number (−11.63 ± 2.3%, P < 0.001), and remaining macrophages stained positive for the anti-inflammatory protein interleukin 10. Genes involved in macrophage attraction (monocyte chemotactic protein [MCP]-1, plasminogen activator urokinase receptor [PLAUR], and colony-stimulating factor [CSF]-3) and hypoxia (hypoxia-inducible factor-1α [HIF-1α]), expression of which increases in obesity and decreases after surgery, were predominantly expressed in the SVF. We show that improvement of the inflammatory profile after weight loss is related to a reduced number of macrophages in scWAT. MCP-1, PLAUR, CSF-3, and HIF-1α may play roles in the attraction of macrophages in scWAT.
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HIF-1 and HIF-1 target genes are overexpressed in adipose tissue of obese individuals and decrease after weight loss.
“Moreover, HIF-1 and HIF-1 target genes are overexpressed in the adipose tissue of obese individuals and decrease after weight loss (25).”
From Hypoxia decreases insulin signaling pathways in adipocytes. (2009) · cites this paper as [25]
Visceral adipose tissue macrophage counts are higher in insulin-resistant obese patients than in lean or insulin-sensitive obese patients.
“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 [114]
Bariatric surgery significantly reduces the elevated visceral adipose tissue macrophage count in insulin-resistant obese patients.
“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 [114]
Adipose loss leads to improvement of the inflammatory profile, with a concomitant reduction of infiltrating macrophages.
“Adipose loss leads to the improvement of the inflammatory profile [11], with a concomitant reduction of infiltrating macrophages [13].”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [13]
The transcriptomic profile of the two main cellular fractions of adipose tissue (adipocytes and SVF cells) obtained from overweight human subjects showed that genes encoding ECM components or related to inflammatory processes were predominantly expressed in the SVF.
“The transcriptomic profile of the two main cellular fractions of adipose tissue (adipocytes and SVF cells) obtained from overweight human subjects [13] showed that genes encoding ECM components or related to inflammatory processes were predominantly expressed in the SVF.”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [13]
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- Authors
- Cancello, R., Henegar, C., Viguerie, N., Taleb, S., Poitou, C., Rouault, C., Coupaye, M., Pelloux, V., Hugol, D., Bouillot, J.-L., Bouloumié, A., Barbatelli, G., Cinti, S., Svensson, P.-A., Barsh, G. S., Zucker, J.-D., Basdevant, A., Langin, D., & Clément, K.
- Affiliations
- Inserm (FR)
- Inserm “Avenir”, Paris 6 University EA3502 and Human Research Center on Nutrition (CRNH), Hôtel Dieu Hospital, AP/HP, Paris, France
- Université Toulouse III - Paul Sabatier (FR)
- Hôtel-Dieu de Paris (FR)
- INSERM UPS U586, Obesity Research Unit, Louis Bugnard Institute, Paul Sabatier University, Toulouse, France
- Marche Polytechnic University (IT)
- University of Gothenburg (SE)
- Stanford Medicine (US)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-08-01
- Volume
- 54
- Issue
- 8
- Pages
- 2277-2286
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2107550410
- Cited by
- 1,164
- References
- 52
- Citations by year
- 2026: 12 · 2025: 23 · 2024: 28 · 2023: 50 · 2022: 38 · 2021: 45 · 2020: 48 · 2019: 42 · 2018: 51 · 2017: 54 · 2016: 59 · 2015: 73 · 2014: 74 · 2013: 110 · 2012: 73
- FWCI
- 42.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Servier
- 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
- macrophage infiltration, white adipose tissue, morbid obesity, bariatric surgery, weight loss, stromal vascular fraction, low-grade inflammation, MCP-1, urokinase receptor, HIF-1α, IL-10, subcutaneous adipose tissue, adipose tissue inflammation
- MeSH terms
- Filgrastim, Adipose Tissue, Adult, Anastomosis, Roux-en-Y, Chemotactic Factors, DNA-Binding Proteins, Female, Humans, Macrophages, Middle Aged, Nuclear Proteins, Obesity, Morbid, Receptors, Cell Surface, Recombinant Proteins, Transcription Factors, Gastric Bypass, Weight Loss, Gene Expression, Granulocyte Colony-Stimulating Factor, Chemokine CCL2, Oligonucleotide Array Sequence Analysis, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Receptors, Urokinase Plasminogen Activator
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