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.

IF 3.9 2区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Lipids in Health and Disease Pub Date : 2025-02-07 DOI:10.1186/s12944-025-02461-5

Dandan Liu, Peipei Tian, Yilin Hou, Tingxue Zhang, Xiaoyu Hou, Lifang Liu, Xiaolong Li, Kunjie Zheng, Chao Wang, Guangyao Song

{"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.","authors":"Dandan Liu, Peipei Tian, Yilin Hou, Tingxue Zhang, Xiaoyu Hou, Lifang Liu, Xiaolong Li, Kunjie Zheng, Chao Wang, Guangyao Song","doi":"10.1186/s12944-025-02461-5","DOIUrl":null,"url":null,"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.","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"40"},"PeriodicalIF":3.9000,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806826/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lipids in Health and Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12944-025-02461-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

游离脂肪酸可能通过ERS-CHOP-C/EBPα信号通路调节高脂饲粮金仓鼠肝脏中11β-羟基类固醇脱氢酶1型的表达。

目的：游离脂肪酸（FFA）可增加局部组织器官11β-羟基类固醇脱氢酶1 （11β-HSD1）的表达。然而，FFA影响11β-HSD1表达的机制尚不清楚。方法：选取SPF级雄性叙利亚金仓鼠24只，随机分为对照组（Con, n = 8）饲喂正常饲粮，高脂饲粮组（n = 16）饲喂12周。在建立高脂血症仓鼠模型成功后，将高脂组进一步分为高脂组（HF）和非诺贝特干预组（Feno）。在口服脂肪耐受试验（OFTT）后，测量血脂和FFA水平。采用Western blot和RT-PCR分析内质网应激（ERS）标志物GRP78、下游关键分子CHOP、C/EBPα和11β-HSD1的表达水平。结果：OFTT后，三组患者FFA水平均呈先降低后升高的趋势，其中HF组最高（p0.05）。HF组肝脏FFA、11β-HSD1、皮质酮水平最高（p0.05）。结论：FFA可能通过ERS-CHOP-C/EBPα信号通路调节高脂喂养金仓鼠肝脏11β-HSD1的表达，从而影响局部皮质酮水平。非诺贝特可能通过降低FFA水平下调局部组织中11β-HSD1和皮质酮的水平。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Lipids in Health and Disease 生物-生化与分子生物学

CiteScore

7.70

自引率

2.20%

发文量

122

审稿时长

3-8 weeks

期刊介绍： Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds. Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.