The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Metabolic Dysfunction Drives a Mechanistically Distinct Proinflammatory Phenotype in Adipose Tissue Macrophages
Open accessAbstract
Adipose tissue macrophage (ATM)-driven inflammation plays a key role in insulin resistance; however, factors activating ATMs are poorly understood. Using a proteomics approach, we show that markers of classical activation are absent on ATMs from obese humans, but readily detectable on airway macrophages of patients with cystic fibrosis, a disease of chronic bacterial infection. Moreover, treating macrophages with glucose, insulin, and palmitate – conditions characteristic of the metabolic syndrome – produces a ‘metabolically-activated’ phenotype distinct from classical activation. Markers of metabolic activation are expressed by pro-inflammatory ATMs in obese humans/mice and are positively correlated with adiposity. Metabolic activation is driven by independent pro- and anti-inflammatory pathways, which regulate balance between cytokine production and lipid metabolism. We identify PPARγ and p62/SQSTM1 as two key proteins that promote lipid metabolism and limit inflammation in metabolically-activated macrophages. Collectively, our data provide important mechanistic insights into pathways that drive the metabolic disease-specific phenotype of macrophages.
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Cites
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · cited 1×
“…by simultaneously exposing macrophages to M1 and M2 stimuli (Figure 1E), suggesting that these markers can report exposure to classical stimuli even in the context of a ''mixed'' macrophage phenotype, which is likely to be present in more complex conditions in vivo (Mosser and Edwards, 2008).”
BackgroundXu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Macrophage plasticity and polarization: in vivo veritas
Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190
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
Abdominal obesity and metabolic syndrome
Després, J.-P., & Lemieux, I. (2006) · Nature · doi:10.1038/nature05488 · Cited by 4,354
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690
Inflammatory links between obesity and metabolic disease
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Cited by
Metabolic regulation of gene expression by histone lactylation
Zhang, D., Tang, Z., Huang, H., Zhou, G., Cui, C., Weng, Y., Liu, W., Kim, S., Lee, S., Perez-Neut, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1678-1 · Cited by 4,371
Self-citationMechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
The metabolic signature of macrophage responses
Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T., & Castegna, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01462 · Cited by 2,021
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
Adipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947
Metadata
- Authors
- Kratz, M., Coats, B. R., Hisert, K. B., Hagman, D., Mutskov, V., Peris, E., Schoenfelt, K. Q., Kuzma, J. N., Larson, I., Billing, P. S., Landerholm, R. W., Crouthamel, M., Gozal, D., Hwang, S., Singh, P. K., & Becker, L.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 20
- Issue
- 4
- Pages
- 614-625
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2016662511
- Cited by
- 815
- References
- 19
- FWCI
- 29.89
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Kratz, M., Coats, B. R., Hisert, K. B., Hagman, D., Mutskov, V., Peris, E., Schoenfelt, K. Q., Kuzma, J. N., Larson, I., Billing, P. S., Landerholm, R. W., Crouthamel, M., Gozal, D., Hwang, S., Singh, P. K., & Becker, L. (2014). Metabolic Dysfunction Drives a Mechanistically Distinct Proinflammatory Phenotype in Adipose Tissue Macrophages. Cell Metabolism. https://doi.org/10.1016/j.cmet.2014.08.010
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