Chronic social defeat stress disrupts regulation of lipid synthesis
Open accessAbstract
Several psychiatric disorders increase the risk of cardiovascular disease, including posttraumatic stress disorder and major depression. While the precise mechanism for this association has not yet been established, it has been shown that certain disorders promote an unfavorable lipid profile. To study the interaction of stress and lipid dysregulation, we utilized chronic social defeat stress (CSDS), a mouse model of chronic stress with features of posttraumatic stress disorder and major depression. Following exposure to CSDS, mice were given access to either regular chow or a Western-style diet high in fat and cholesterol (HFD). The combination of social stress and HFD resulted in significant perturbations in lipid regulation, including two key features of the metabolic syndrome: increased plasma levels of non-HDL cholesterol and intrahepatic accumulation of triglycerides. These effects were accompanied by a number of changes in the expression of hepatic genes involved in lipid regulation. Transcriptional activity of LXR, SREBP1c, and ChREBP were significantly affected by exposure to HFD and CSDS. We present CSDS as a model of social stress induced lipid dysregulation and propose that social stress alters lipid metabolism by increasing transcriptional activity of genes involved in lipid synthesis.
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The metabolic disturbances associated with susceptibility have been linked to alterations in orexin, ghrelin and lipid regulation.
“Interestingly, the metabolic disturbances associated with susceptibility have been linked to alterations in orexin, ghrelin and lipid regulation23–26.”
From A standardized protocol for repeated social defeat stress in mice (2011) · cites this paper as [24]
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- Authors
- Chuang, J.-C., Cui, H., Mason, B. L., Mahgoub, M., Bookout, A. L., Yu, H. G., Perello, M., Elmquist, J. K., Repa, J. J., Zigman, J. M., & Lutter, M.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Lutter, Michael
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 51
- Issue
- 6
- Pages
- 1344-1353
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC3035497
- OpenAlex
- W2129714293
- Cited by
- 126
- References
- 6
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 9 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 13 · 2016: 2 · 2015: 11 · 2014: 10 · 2013: 13 · 2012: 6
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Klarman Family Foundation
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (DK53301)
- National Institute of Mental Health (K08MH084058)
- National Institute of Diabetes and Digestive and Kidney Diseases (PL1DK081182, RL1DK081185, R01DK071320, K08DK068069, RL1DK081182, R37DK053301)
- National Institute of Dental and Craniofacial Research (UL1DE019584)
- National Center for Research Resources (UL1RR024923)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- chronic social defeat stress, lipid metabolism, lipogenesis, non-HDL cholesterol, hepatic triglycerides, metabolic syndrome, post-traumatic stress disorder, major depressive disorder, liver X receptor, SREBP-1c, ChREBP, hepatic gene expression, cardiovascular risk
- MeSH terms
- Animals, Cholesterol, Chronic Disease, Depression, Dietary Fats, Disease Models, Animal, Fatty Acids, Nonesterified, Insulin Resistance, Lipids, Liver, Male, Mice, Inbred C57BL, Stress, Physiological, Stress Disorders, Post-Traumatic, Time Factors, Triglycerides, Mice
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