Free fatty acids may regulate the expression of 11β-hydroxysteroid dehydrogenase type 1 in the liver of high-fat diet golden hamsters through the ERS-CHOP-C/EBPα signaling pathway
Abstract Objective Free fatty acids (FFA) can increase the expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in local tissues and organs. However, the mechanism underlying the effect of FFA on 11β-HSD1 expression remains unclear. Methods A total of 24 male Syrian golden hamsters (SPF grade...
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BMC
2025-02-01
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| Series: | Lipids in Health and Disease |
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| Online Access: | https://doi.org/10.1186/s12944-025-02461-5 |
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| author | Dandan Liu Peipei Tian Yilin Hou Tingxue Zhang Xiaoyu Hou Lifang Liu Xiaolong Li Kunjie Zheng Chao Wang Guangyao Song |
| author_facet | Dandan Liu Peipei Tian Yilin Hou Tingxue Zhang Xiaoyu Hou Lifang Liu Xiaolong Li Kunjie Zheng Chao Wang Guangyao Song |
| author_sort | Dandan Liu |
| collection | DOAJ |
| description | Abstract Objective Free fatty acids (FFA) can increase the expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in local tissues and organs. However, the mechanism underlying the effect of FFA on 11β-HSD1 expression remains unclear. Methods A total of 24 male Syrian golden hamsters (SPF grade) were selected and randomly divided into a control group (Con, n = 8) fed a normal diet, and a high-fat diet group (n = 16) fed for 12 weeks. After successfully establishing the hyperlipidemia hamster model, the high-fat group was further divided into a high-fat group (HF) and a fenofibrate intervention group (Feno). Following an oral fat tolerance test (OFTT), blood lipids and FFA levels were measured. The expression levels of endoplasmic reticulum stress (ERS) marker GRP78, downstream key molecule CHOP, C/EBPα, and 11β-HSD1 were analyzed using Western blot and RT-PCR. Results After OFTT, FFA levels in all three groups initially decreased and then increased, with the highest levels observed in the HF group (Ps < 0.05). FFA levels in the Feno group were comparable to those in the Con group (P > 0.05). Hepatic FFA, 11β-HSD1, and corticosterone levels were highest in the HF group (Ps < 0.05), while the Feno group showed no significant difference compared to the Con group (Ps > 0.05). Hepatic 11β-HSD1 and corticosterone levels were positively correlated with FFA levels (Ps < 0.05). Western blot and RT-PCR results indicated higher GRP78, CHOP, C/EBPα, and 11β-HSD1 protein and mRNA expression in the HF group compared to the Con group (Ps < 0.05). Fenofibrate intervention reduced FFA levels and downregulated these indicators in the Feno group compared to the HF group (Ps < 0.05). Conclusion FFA may regulate the expression of hepatic 11β-HSD1 in high-fat-fed golden hamsters via the ERS-CHOP-C/EBPα signaling pathway, thereby affecting local corticosterone levels. Fenofibrate may downregulate the levels of 11β-HSD1 and corticosterone in local tissues by reducing FFA levels. |
| format | Article |
| id | doaj-art-1675b22161ef451aa85d6db080c162a3 |
| institution | Kabale University |
| issn | 1476-511X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Lipids in Health and Disease |
| spelling | doaj-art-1675b22161ef451aa85d6db080c162a32025-02-09T12:52:37ZengBMCLipids in Health and Disease1476-511X2025-02-0124111510.1186/s12944-025-02461-5Free fatty acids may regulate the expression of 11β-hydroxysteroid dehydrogenase type 1 in the liver of high-fat diet golden hamsters through the ERS-CHOP-C/EBPα signaling pathwayDandan Liu0Peipei Tian1Yilin Hou2Tingxue Zhang3Xiaoyu Hou4Lifang Liu5Xiaolong Li6Kunjie Zheng7Chao Wang8Guangyao Song9Department of Internal Medicine, Hebei Medical UniversityDepartment of Internal Medicine, Hebei Medical UniversityDepartment of Internal Medicine, Hebei Medical UniversityDepartment of Internal Medicine, Hebei Medical UniversityDepartment of Internal Medicine, Hebei Medical UniversityDepartment of Internal Medicine, Hebei Medical UniversityDepartment of Internal Medicine, Hebei Medical UniversityDepartment of Internal Medicine, Hebei Medical UniversityHebei Key Laboratory of Metabolic Diseases, Hebei General HospitalDepartment of Internal Medicine, Hebei Medical UniversityAbstract Objective Free fatty acids (FFA) can increase the expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in local tissues and organs. However, the mechanism underlying the effect of FFA on 11β-HSD1 expression remains unclear. Methods A total of 24 male Syrian golden hamsters (SPF grade) were selected and randomly divided into a control group (Con, n = 8) fed a normal diet, and a high-fat diet group (n = 16) fed for 12 weeks. After successfully establishing the hyperlipidemia hamster model, the high-fat group was further divided into a high-fat group (HF) and a fenofibrate intervention group (Feno). Following an oral fat tolerance test (OFTT), blood lipids and FFA levels were measured. The expression levels of endoplasmic reticulum stress (ERS) marker GRP78, downstream key molecule CHOP, C/EBPα, and 11β-HSD1 were analyzed using Western blot and RT-PCR. Results After OFTT, FFA levels in all three groups initially decreased and then increased, with the highest levels observed in the HF group (Ps < 0.05). FFA levels in the Feno group were comparable to those in the Con group (P > 0.05). Hepatic FFA, 11β-HSD1, and corticosterone levels were highest in the HF group (Ps < 0.05), while the Feno group showed no significant difference compared to the Con group (Ps > 0.05). Hepatic 11β-HSD1 and corticosterone levels were positively correlated with FFA levels (Ps < 0.05). Western blot and RT-PCR results indicated higher GRP78, CHOP, C/EBPα, and 11β-HSD1 protein and mRNA expression in the HF group compared to the Con group (Ps < 0.05). Fenofibrate intervention reduced FFA levels and downregulated these indicators in the Feno group compared to the HF group (Ps < 0.05). Conclusion FFA may regulate the expression of hepatic 11β-HSD1 in high-fat-fed golden hamsters via the ERS-CHOP-C/EBPα signaling pathway, thereby affecting local corticosterone levels. Fenofibrate may downregulate the levels of 11β-HSD1 and corticosterone in local tissues by reducing FFA levels.https://doi.org/10.1186/s12944-025-02461-5Free fatty acids11β-hydroxysteroid dehydrogenase 1Endoplasmic reticulum stressCCAAT/enhancer-binding protein homologous proteinCCAAT/enhancer-binding protein αCorticosterone |
| spellingShingle | Dandan Liu Peipei Tian Yilin Hou Tingxue Zhang Xiaoyu Hou Lifang Liu Xiaolong Li Kunjie Zheng Chao Wang Guangyao Song Free fatty acids may regulate the expression of 11β-hydroxysteroid dehydrogenase type 1 in the liver of high-fat diet golden hamsters through the ERS-CHOP-C/EBPα signaling pathway Lipids in Health and Disease Free fatty acids 11β-hydroxysteroid dehydrogenase 1 Endoplasmic reticulum stress CCAAT/enhancer-binding protein homologous protein CCAAT/enhancer-binding protein α Corticosterone |
| title | Free fatty acids may regulate the expression of 11β-hydroxysteroid dehydrogenase type 1 in the liver of high-fat diet golden hamsters through the ERS-CHOP-C/EBPα signaling pathway |
| title_full | Free fatty acids may regulate the expression of 11β-hydroxysteroid dehydrogenase type 1 in the liver of high-fat diet golden hamsters through the ERS-CHOP-C/EBPα signaling pathway |
| title_fullStr | Free fatty acids may regulate the expression of 11β-hydroxysteroid dehydrogenase type 1 in the liver of high-fat diet golden hamsters through the ERS-CHOP-C/EBPα signaling pathway |
| title_full_unstemmed | Free fatty acids may regulate the expression of 11β-hydroxysteroid dehydrogenase type 1 in the liver of high-fat diet golden hamsters through the ERS-CHOP-C/EBPα signaling pathway |
| title_short | Free fatty acids may regulate the expression of 11β-hydroxysteroid dehydrogenase type 1 in the liver of high-fat diet golden hamsters through the ERS-CHOP-C/EBPα signaling pathway |
| title_sort | free fatty acids may regulate the expression of 11β hydroxysteroid dehydrogenase type 1 in the liver of high fat diet golden hamsters through the ers chop c ebpα signaling pathway |
| topic | Free fatty acids 11β-hydroxysteroid dehydrogenase 1 Endoplasmic reticulum stress CCAAT/enhancer-binding protein homologous protein CCAAT/enhancer-binding protein α Corticosterone |
| url | https://doi.org/10.1186/s12944-025-02461-5 |
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