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Chronic glucocorticoid treatment induced circadian clock disorder leads to lipid metabolism and gut microbiota alterations in rats
Abstract
Aim Glucocorticoids (GCs), steroid hormones synthetized by the adrenal gland, are regulated by circadian cycles, and dysregulation of GC signaling can lead to the development of metabolic syndrome. The effects and potential mechanism of GCs in physiology were investigated in the present study.Main methods Male Wistar rats were orally administered dexamethasone sodium phosphate (DEX, 0.01 and 0.05mg/kg body weight per day) for 7weeks.Key finding DEX treatment attenuated body weight gain and reduced food intake, whereas it induced the accumulation of fat. Administration of DEX induced dysregulation of the expression of lipogenic genes in both fat and liver. Moreover, the mRNA levels of genes related to mitochondrial biogenesis and function were significantly downregulated in the liver and fat of DEX-treated rats. Furthermore, DEX treatment caused a significant reduction in the richness and diversity of the microbiota in the colon, as assessed using high-throughput sequencing of the 16s rRNA gene V3-V4 region, an increase in inflammatory cell infiltration, and a decrease in mucus secretion in the colon. Additionally, DEX administration induced phase shift or loss of circadian rhythmicity of clock-related genes in peripheral tissues. These results were associated with higher serum corticosterone levels and upregulation of GC receptor (GR) expression in peripheral tissues.Significance Our findings indicate that long-term administration of GC caused lipid accumulation, changes in the structure of the intestinal flora, and reduced colonic mucus secretion in vivo. The mechanism of these physiological changes may involve a circadian rhythm disorder and dysregulation of GR expression.
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“Experimental administration of glucocorticoid synchronizes the peripheral clocks located in liver, muscle, and adipose tissue which are the major storage sites for glycogen, protein, and fat, respectively, as well as other metabolically relevant organs such as pancreas and gut [60–63].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [61]
In the citing paper
“This rhythm is important for its action because cortisol, not melatonin, is recognized to be the key metabolic central synchronizing signal [60–62].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [61]
In the citing paper
“Regarding the effects of glucocorticoids on the composition and functioning of the microbiota, some studies have indicated microbiota disruption, while others have shown beneficial effects, which likely depend on the degree of exposure (dose and period) and the type of glucocorticoid studied (434–437)”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [434]
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Metadata
- Authors
- Wu, T., Yang, L., Jiang, J., Ni, Y., Zhu, J., Zheng, X., Wang, Q., Lu, X., & Fu, Z.
- Affiliations
- Zhejiang University of Technology (CN)
- Corresponding author
- Fu, Zhengwei
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 192
- Pages
- 173-182
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2775302672
- Cited by
- 126
- References
- 53
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 22 · 2023: 15 · 2022: 15 · 2021: 14 · 2020: 14 · 2019: 13 · 2018: 12
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31200890)
- Open Research Fund Program of the Collaborative Innovation Center of Membrane Separation and Water Treatment, Zhejiang Province Public Welfare Research Project (2015C33178)
- Scientific Innovation Program for University Students in Zhejiang Province (2014R403060)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- glucocorticoids, dexamethasone, circadian clock, circadian rhythm disorders, lipid metabolism, gut microbiota, metabolic syndrome, lipogenic genes, mitochondrial biogenesis, colonic inflammation, corticosterone, glucocorticoid receptor, adipose tissue, liver
- MeSH terms
- Gastrointestinal Microbiome, Adipose Tissue, Animals, Cecum, Colon, Corticosterone, Dexamethasone, Eating, Glucose Tolerance Test, Glycolipids, Liver, Male, Mitochondria, Receptors, Glucocorticoid, Weight Gain, Rats, Wistar, Lipid Metabolism, Rats, Circadian Clocks
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