Diet Induction of Monocyte Chemoattractant Protein‐1 and its Impact on Obesity
Open accessAbstract
Objective: To examine the effect of a high‐fat diet on gene expression in adipose tissues and to determine induction kinetics of adipose monocyte chemoattractant protein‐1 and −3 (MCP‐1 and MCP‐3) in diet‐induced obesity (DIO) and the effect of a lack of MCP‐1 signaling on DIO susceptibility and macrophage recruitment into adipose tissue. Research Methods and Procedures: Obese and lean adipose tissues were profiled for expression changes. The time‐course of MCP‐1 and MCP‐3 expression was examined by reverse transcriptase‐polymerase chain reaction. Plasma MCP‐1 levels were determined by enzyme‐linked immunosorbent assay (ELISA). Chemokine receptor‐2 (CCR2) knockout mice were placed on the high‐fat diet to determine DIO susceptibility. Macrophage infiltration in adipose tissue was examined by immunohistochemistry with F4/80 antibody. Results: DIO elevated adipose expression of many inflammatory genes, including MCP‐1 and MCP‐3. Adipose MCP‐1 and MCP‐3 mRNA levels increased within 7 days of starting a high‐fat diet, with elevation of plasma MCP‐1 detected after 4 weeks on the diet. The induction of MCP‐1 and MCP‐3 expression preceded that of tumor necrosis factor‐α. The elevated plasma MCP‐1 concentration in obese mice was partially reversed by treatment with AM251. No change in DIO susceptibility and macrophage accumulation in adipose tissue were observed in CCR2 knockout mice, which lack the MCP‐1 receptor CCR2. Discussion: A high‐fat diet elevated adipose expression of inflammatory genes, including early induction of MCP‐1 and MCP‐3, supporting the view that obese adipose tissues contribute to systemic inflammation. However, despite increased MCP‐1 in obesity, disruption of MCP‐1 signaling did not confer resistance to DIO in mice or reduce adipose tissue macrophage infiltration.
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Adipose tissue macrophages (ATMs) comprise a significant proportion of adipose tissue cells in lean and obese states.
“Adipose tissue macrophages (ATM) have been shown to comprise a significant proportion of the cellular component of adipose tissue in both lean and obese states [60–63].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [61]
Other studies found no effect of Ccr2 or Ccl2 knockout on total macrophage recruitment.
“In contrast, other studies have found no effect of KO of Ccr2 or Ccl2 on total macrophage recruitment (119, 122, 123) or insulin sensitivity (122, 123).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [119]
Ccl2 and/or Ccr2 expression is increased in obese adipose tissue.
“Ccl2 and/or Ccr2 expression is increased in obese adipose tissue (119-122)”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [119]
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- Authors
- Chen, A., Mumick, S., Zhang, C., Lamb, J., Dai, H., Weingarth, D., Mudgett, J., Chen, H., MacNeil, D. J., Reitman, M. L., & Qian, S.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Qian, Su
- ORCID
- Venue
- Obesity Research
- Publisher
- Wiley
- Published
- 2005-08
- Volume
- 13
- Issue
- 8
- Pages
- 1311-1320
- ISSN
- 1071-7323 (ISSN-L)
- 1550-8528
- OpenAlex
- W1973259074
- Cited by
- 231
- References
- 26
- Citations by year
- 2025: 2 · 2024: 9 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 12 · 2015: 12 · 2014: 9 · 2013: 22 · 2012: 15
- FWCI
- 12.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Obesity Research (publishedVersion)
- PubMed (publishedVersion)
- 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
- diet-induced obesity, MCP-1, MCP-3, adipose tissue inflammation, chemokine expression, CCR2 knockout mice, TNF-α, AM251, high-fat diet, systemic inflammation
- MeSH terms
- CD68 Molecule, Animals, Dietary Fats, Macrophages, Male, Mice, Inbred C57BL, Obesity, RNA, Messenger, Tumor Necrosis Factor-alpha, Antigens, Differentiation, Myelomonocytic, Signal Transduction, Antigens, CD, Adipocytes, Mice, Knockout, Inflammation Mediators, Chemokine CCL2, Receptors, Chemokine, Gene Expression Profiling, Carboxypeptidases A, Mice, Receptors, CCR2
About these checks
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