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Very Low Density Lipoprotein Receptor (VLDLR) Expression Is a Determinant Factor in Adipose Tissue Inflammation and Adipocyte-Macrophage Interaction
Abstract
Obesity is associated with adipose tissue remodeling, characterized by adipocyte hypertrophy and macrophage infiltration. Previously, we have shown that very low density lipoprotein receptor (VLDLR) is virtually absent in preadipocytes but is strongly induced during adipogenesis and actively participates in adipocyte hypertrophy. In this study, we investigated the role of VLDLR in adipose tissue inflammation and adipocyte-macrophage interactions in wild type and VLDLR-deficient mice fed a high fat diet. The results show that VLDLR deficiency reduced high fat diet-induced inflammation and endoplasmic reticulum (ER) stress in adipose tissue in conjunction with reduced macrophage infiltration, especially those expressing pro-inflammatory markers. In adipocyte culture, VLDLR deficiency prevented adipocyte hypertrophy and strongly reduced VLDL-induced ER stress and inflammation. Likewise, cultures of primary peritoneal macrophages show that VLDLR deficiency reduced lipid accumulation and inflammation but did not alter chemotactic response of macrophages to adipocyte signals. Moreover, VLDLR deficiency tempered the synergistic inflammatory interactions between adipocytes and macrophages in a co-culture system. Collectively, these results show that VLDLR contributes to adipose tissue inflammation and mediates VLDL-induced lipid accumulation and induction of inflammation and ER stress in adipocytes and macrophages.
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VLDLR mediates VLDL binding and lipid uptake in extrahepatic tissues and plays a vital role in lipoprotein metabolism.
“It is originally recognized to mediate VLDL binding and lipid uptake in extrahepatic tissues, where it plays a vital role in lipoprotein metabolism (2, 3).”
From ADAM17 mediates ectodomain shedding of the soluble VLDL receptor fragment in the retinal epithelium (2021) · cites this paper as [3]
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“Investigations using in vitro co-culture systems have demonstrated reciprocal impacts of adipocytes and macrophages and also highlighted the contributions of these cells in inflammation (3, 36).”
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Self-citationSaraswathi, V., & Hasty, A. H. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600159-jlr200 · Cited by 95
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ADAM17 mediates ectodomain shedding of the soluble VLDL receptor fragment in the retinal epithelium
Ma, X., Takahashi, Y., Wu, W., Liang, W., Chen, J., Chakraborty, D., Li, Y., Du, Y., Benyajati, S., & Ma, J.-X. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101185 · Cited by 9
Metadata
- Authors
- Nguyen, A., Tao, H., Metrione, M., & Hajri, T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 289
- Issue
- 3
- Pages
- 1688-1703
- ISSN
- 0021-9258
- Cited by
- 65
- References
- 3
- Language
- en
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