SCAP deficiency facilitates obesity and insulin resistance through shifting adipose tissue macrophage polarizationopen access
- Authors
- Lee, Jae-Ho; Hee Lee, Sun; Lee, Eun-Ho; Cho, Jeong-Yong; Song, Dae-Kyu; Jae Lee, Young; Kyu Kwon, Taeg; Oh, Byung-Chul; Won Cho, Kae; Osborne, Timothy F.; Jeon, Tae-Il; Im, Seung-Soon
- Issue Date
- Mar-2023
- Publisher
- Cairo University
- Keywords
- SCAP; White adipose tissue; Macrophages; Cholesterol 25-hydroxylase; Cholesterol efflux
- Citation
- Journal of Advanced Research, v.45, pp 1 - 13
- Pages
- 13
- Journal Title
- Journal of Advanced Research
- Volume
- 45
- Start Page
- 1
- End Page
- 13
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/21666
- DOI
- 10.1016/j.jare.2022.05.013
- ISSN
- 2090-1232
2090-1224
- Abstract
- Results: We found that fat accumulation and the appearance of proinflammatory M1 macrophages were both higher in HFHS-fed SCAP mKO mice relative to floxed control mice. We traced the effect to a defect in the lipopolysaccharide-mediated increase in SREBP-1a that occurs in control but not SCAP mKO mice. Mechanistically, SREBP-1a increased expression of cholesterol 25-hydroxylase transcription, resulting in an increase in the production of 25-hydroxycholesterol (25-HC), an endogenous agonist of liver X receptor alpha (LXRa) which increased expression of cholesterol efflux to limit cholesterol accu-mulation and M1 polarization. In the absence of SCAP mediated activation of SREBP-1a, increased M1 macrophage polarization resulted in reduced cholesterol efflux downstream from 25-HC-dependent LXRa activation. Conclusion: Overall, the activation of the SCAP-SREBP-1a pathway in macrophages may provide a novel therapeutic strategy that ameliorates obesity by controlling cholesterol homeostasis in ATMs. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
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