The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins
Open accessAbstract
Obesity leads to a proinflammatory state with immune responses that include infiltration of adipose tissue with macrophages. These macrophages are believed to alter insulin sensitivity in adipocytes, but the mechanisms that underlie this effect have not been characterized. We have explored the interaction between macrophages and adipocytes in the context of both indirect and direct coculture. Macrophage-secreted factors blocked insulin action in adipocytes via downregulation of GLUT4 and IRS-1, leading to a decrease in Akt phosphorylation and impaired insulin-stimulated GLUT4 translocation to the plasma membrane. GLUT1 was upregulated with a concomitant increase in basal glucose uptake. These changes recapitulate those seen in adipose tissue from insulin-resistant humans and animal models. TNF-alpha-neutralizing antibodies partially reversed the insulin resistance produced by macrophage-conditioned media. Peritoneal macrophages and macrophage-enriched stromal vascular cells from adipose tissue also attenuated responsiveness to insulin in a manner correlating with inflammatory cytokine secretion. Adipose tissue macrophages from obese mice have an F4/80(+)CD11b(+)CD68(+)CD14(-) phenotype and form long cellular extensions in culture. Peritoneal macrophages take on similar characteristics in direct coculture with adipocytes and induce proinflammatory cytokines, suggesting that macrophage activation state is influenced by contact with adipocytes. Thus both indirect/secreted and direct/cell contact-mediated factors derived from macrophages influence insulin sensitivity in adipocytes.
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“It downregulates the major insulin-responsive glucose transporter GLUT4 and inhibits insulin-dependent tyrosine phosphorylation of the insulin receptor and IRS-1 through ceramide production (70,71).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [70]
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Cites
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Cited by
Sorted by citations
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
Self-citationMacrophage-specific PPARγ controls alternative activation and improves insulin resistance
Odegaard, J. I., Ricardo-Gonzalez, R. R., Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., Eagle, A. R., Vats, D., Brombacher, F., Ferrante, A. W., et al. (2007) · Nature · doi:10.1038/nature05894 · Cited by 2,107
Macrophage-mediated inflammation in metabolic disease
Chawla, A., Nguyen, K. D., & Goh, Y. P. S. (2011) · Nature reviews. Immunology · doi:10.1038/nri3071 · Cited by 1,314
Clinical Update: Cardiovascular Disease in Diabetes Mellitus
Wang, C. C. L., Hess, C. N., Hiatt, W. R., & Goldfine, A. B. (2016) · Circulation · doi:10.1161/circulationaha.116.022194 · Cited by 1,222
Lumeng, C. N., DeYoung, S. M., Bodzin, J. L., & Saltiel, A. R. (2007) · Diabetes · doi:10.2337/db06-1076 · Cited by 1,016
Metadata
- Authors
- Lumeng, C. N., Deyoung, S. M., & Saltiel, A. R.
- Affiliations
- University of Michigan (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2007-01
- Volume
- 292
- Issue
- 1
- Pages
- E166-E174
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC3888778
- OpenAlex
- W2086073611
- Cited by
- 359
- References
- 68
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 7 · 2023: 11 · 2022: 13 · 2021: 19 · 2020: 22 · 2019: 13 · 2018: 14 · 2017: 28 · 2016: 19 · 2015: 19 · 2014: 31 · 2013: 28 · 2012: 25
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 60591, R01DK060591, K08DK078851)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007513)
- 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
- macrophages, adipocytes, insulin resistance, GLUT4, IRS-1, Akt phosphorylation, GLUT1, glucose transport, TNF-α, adipose tissue inflammation, obesity, macrophage activation, stromal vascular cells, inflammatory cytokines
- MeSH terms
- Adipose Tissue, Animals, Cells, Cultured, Insulin, Insulin Resistance, Macrophages, Male, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha, Signal Transduction, Culture Media, Conditioned, Stromal Cells, Adipocytes, Coculture Techniques, Protein Transport, 3T3-L1 Cells, Glucose Transport Proteins, Facilitative, Glucose Transporter Type 4, Mice
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