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β-Arrestin-1 Protein Represses Adipogenesis and Inflammatory Responses through Its Interaction with Peroxisome Proliferator-activated Receptor-γ (PPARγ)
Open accessAbstract
One of the master regulators of adipogenesis and macrophage function is peroxisome proliferator-activated receptor-γ (PPARγ). Here, we report that a deficiency of β-arrestin-1 expression affects PPARγ-mediated expression of lipid metabolic genes and inflammatory genes. Further mechanistic studies revealed that β-arrestin-1 interacts with PPARγ. β-Arrestin-1 suppressed the formation of a complex between PPARγ and 9-cis-retinoic acid receptor-α through its direct interaction with PPARγ. The interaction of β-arrestin-1 with PPARγ repressed PPARγ/9-cis-retinoic acid receptor-α function but promoted PPARγ/nuclear receptor corepressor function in PPARγ-mediated adipogenesis and inflammatory gene expression. Consistent with these results, a deficiency of β-arrestin-1 binding to PPARγ abolished its suppression of PPARγ-dependent adipogenesis and inflammatory responses. These results indicate that the regulation of PPARγ by β-arrestin-1 is critical. Furthermore, in vivo expression of β-arrestin-1 (but not the binding-deficient mutant) significantly repressed adipogenesis, macrophage infiltration, and diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Therefore, our findings not only reveal a molecular mechanism for the modulation of obesity by β-arrestin-1 but also suggest a potential tactical approach against obesity and its associated metabolic disorders.
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“It appears that both G-protein signal activation and the beta-arrestin pathway may facilitate weight loss by inhibiting adipogenesis and inflammatory response [23,27].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [27]
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Cites
Dignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor
Tontonoz, P., Hu, E., & Spiegelman, B. M. (1994) · Cell · doi:10.1016/0092-8674(94)90006-x · Cited by 3,564
Adipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170
Macrophage-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
Fat and Beyond: The Diverse Biology of PPARγ
Tontonoz, P., & Spiegelman, B. M. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061307.091829 · Cited by 2,085
PPARs and the complex journey to obesity
Evans, R. M., Barish, G. D., & Wang, Y.-X. (2004) · Nature Medicine · doi:10.1038/nm1025 · Cited by 1,650
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., Charo, I., Leibel, R. L., & Jr., A. W. F. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335 · Cited by 1,497
Lehrke, M., & Lazar, M. A. (2005) · Cell · doi:10.1016/j.cell.2005.11.026 · Cited by 1,472
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Metadata
- Authors
- Zhuang, L.-N., Hu, W.-X., Xin, S.-M., Zhao, J., & Pei, G.
- Affiliations
- Chinese Academy of Sciences (CN)
- Tongji University (CN)
- Corresponding author
- Zhao, Jian
- Pei, Gang
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 286
- Issue
- 32
- Pages
- 28403-28413
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3151083
- OpenAlex
- W2088343196
- Cited by
- 34
- References
- 41
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 1
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sanofi
- National Natural Science Foundation of China (90713047, 2007CB947100, 30871285)
- Chinese Academy of Sciences (XDA01010302)
- Directorate for Biological Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- β-arrestin1, PPARγ, adipogenesis, inflammation, nuclear receptor corepressor, protein-protein interaction, macrophage infiltration, diet-induced obesity, glucose tolerance, insulin sensitivity, lipid metabolism, obesity
- MeSH terms
- beta-Arrestins, beta-Arrestin 1, Animals, Diet, Gene Expression Regulation, Inflammation, Obesity, Protein Binding, Mice, Knockout, Arrestins, Retinoid X Receptors, PPAR gamma, Adipogenesis, Mice
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