Abstract | Background: Chronic unpredictable mild stress (CUMS) has been shown to exacerbate atherosclerosis, but the underlying mechanism remains unknown. Adipose tissue is an energy storage organ and the largest endocrine organ in the human body, playing a key role in the development of cardiovascular disease. In this research, it was hypothesized that CUMS may exacerbate the development of atherosclerosis by inducing the hypertrophy and dysfunction of white adipocytes. Methods: Results: CUMS aggravated vascular atherosclerotic lesions in ApoE-/- mice. It decreased body weight while increasing the percentage of WAT. The serological results indicated that the concentration of HDL decreased in CUMS mice. Notably, adipocyte hypertrophy increased, whereas the mRNA levels of Pparg and its target genes (Slc2a4 (encodes for GLUT4), Adipoq, and Plin1) decreased. Further investigation revealed that CUMS increased subcutaneous inguinal WAT (iWAT) lipid synthesis and adipocyte inflammation while decreasing lipid hydrolysis and the expression of HDL-associated protein ApoA-I. Moreover, CUMS aggravated insulin resistance in mice and inhibited the insulin pathway in iWAT. Conclusions: These findings indicated that CUMS induces adipose tissue dysfunction via a mechanism that leads to dyslipidemia, increased inflammation, and insulin resistance in the body, thereby exacerbating atherosclerosis. Notably, CUMS that is involved in decreasing the expression of HDL-associated proteins in adipose tissue may be a crucial link between adipose hypertrophy and advanced atherosclerosis. This study reveals a novel mechanism via which CUMS exacerbates atherosclerosis from the novel perspective of abnormal adipose function and identifies a novel potential therapeutic target for this disease.
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Authors | Min Mao, Yalan Deng, Li Wang, Gexin Zhao, Ruomei Qi, Huan Gong, Tao Shen, Yitian Xu, Deping Liu, Beidong Chen |
Journal | PeerJ
(PeerJ)
Vol. 11
Pg. e16029
( 2023)
ISSN: 2167-8359 [Electronic] United States |
PMID | 37692113
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2023 Mao et al. |
Topics |
- Animals
- Mice
- Adipocytes, White
- Adipose Tissue
- Atherosclerosis
(etiology)
- Insulin Resistance
- Obesity
- Mice, Knockout, ApoE
- Stress, Psychological
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