Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity
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Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo . In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese.
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The distinction between obesity-induced features occurring in the entire adipocyte population versus specific adipocyte subpopulations may explain the outstanding effectiveness of PPARγ agonists, such as thiazolidinediones, in improving adipose function and glucose homeostasis, surpassing the effects of other anti-inflammatory or anti-stress reagents.
“The distinctions between obesity-induced features occurring in the entire adipocyte population versus specific adipocyte subpopulations may explain the outstanding effectiveness of PPARγ agonists, such as thiazolidinediones, in improving adipose function and glucose homeostasis (Soccio et al., 2014), surpassing the effects of other anti-inflammatory or anti-stress reagents (Kraakman et al., 2015;”
From Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity (2025) · cites this paper as Chen et al., 2016
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- Authors
- Chen, Y., Wu, Z., Zhao, S., & Xiang, R.
- Affiliations
- Second Xiangya Hospital of Central South University (CN)
- Central South University (CN)
- Corresponding author
- Xiang, Rong
- Venue
- Scientific Reports
- Published
- 2016-06-08
- Volume
- 6
- Issue
- 1
- Pages
- 27486-27486
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4897685
- OpenAlex
- W2412535284
- Cited by
- 80
- References
- 31
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 12 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 7 · 2017: 8 · 2016: 2
- FWCI
- 8.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- endoplasmic reticulum stress, chemical chaperones, 4-phenylbutyric acid, tauroursodeoxycholic acid, obesity, adipose tissue inflammation, high-fat diet, adipokine secretion, NF-κB signaling, IκB kinase, free cholesterol, inflammatory cytokines, metabolic disorders
- MeSH terms
- Adipose Tissue, Animals, Inflammation, Male, Mice, Inbred C57BL, Obesity, NF-kappa B, Molecular Chaperones, 3T3-L1 Cells, Mice, Diet, High-Fat, Endoplasmic Reticulum Stress
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