Lishuang Li, Xing Ren, Xinyu Gao, Yujia Zhao, Yuman Ma, Junxiao Gong, Shuo Yang, Yanan Sun, Yi Wang
{"title":"多组学分析揭示了鹅去氧胆酸在脂肪酸代谢和脂质稳态中的调节作用。","authors":"Lishuang Li, Xing Ren, Xinyu Gao, Yujia Zhao, Yuman Ma, Junxiao Gong, Shuo Yang, Yanan Sun, Yi Wang","doi":"10.1186/s12944-025-02656-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the regulatory role and mechanisms of chenodeoxycholic acid (CDCA) on lipid metabolism, and to evaluate its therapeutic potential in lipid metabolism-related diseases such as acne, seborrheic alopecia, and prostate cancer, with the aim of identifying safer and more sustainable treatment alternatives.</p><p><strong>Methods: </strong>Lipid-overproduction models were established using RM-1 (murine prostate cancer cells) and primary sebaceous gland cells, stimulated by linoleic acid (LA) and dihydrotestosterone (DHT), respectively. CDCA's mechanisms were explored using transcriptomics, proteomics, and fatty acid-targeted metabolomics. In vivo validation was conducted via intradermal injection of CDCA into the sebaceous gland area of golden hamsters to assess its effect on sebaceous lipid metabolism.</p><p><strong>Results: </strong>CDCA significantly reduced intracellular lipid accumulation in both murine prostate cancer cells (RM-1) and primary sebaceous gland cells, and suppressed the expression of the androgen receptor (AR), along with the downregulation of key lipogenic enzymes (SREBF1, FASN, FADS2). Mitochondrial membrane potential was restored in CDCA-treated cells. Multi-omics analyses revealed that CDCA modulated fatty acid biosynthesis and degradation, energy metabolism, mitochondrial function, and Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) signaling. Lipidomic profiling demonstrated a shift from saturated to unsaturated fatty acid dominance after CDCA treatment. In vivo, CDCA decreased sebaceous lipid accumulation and downregulated PPAR-γ expression in golden hamsters.</p><p><strong>Conclusion: </strong>CDCA exerted multifaceted regulatory effects on lipid metabolism, hormone signaling, and mitochondrial dynamics. These effects contributed to the maintenance of sebaceous gland homeostasis and supported the development of innovative and potentially more biocompatible therapies for lipid-related disorders.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"238"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261562/pdf/","citationCount":"0","resultStr":"{\"title\":\"Multiomics analysis revealed the regulatory role of chenodeoxycholic acid in fatty acid metabolism and lipid homeostasis.\",\"authors\":\"Lishuang Li, Xing Ren, Xinyu Gao, Yujia Zhao, Yuman Ma, Junxiao Gong, Shuo Yang, Yanan Sun, Yi Wang\",\"doi\":\"10.1186/s12944-025-02656-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>This study aimed to investigate the regulatory role and mechanisms of chenodeoxycholic acid (CDCA) on lipid metabolism, and to evaluate its therapeutic potential in lipid metabolism-related diseases such as acne, seborrheic alopecia, and prostate cancer, with the aim of identifying safer and more sustainable treatment alternatives.</p><p><strong>Methods: </strong>Lipid-overproduction models were established using RM-1 (murine prostate cancer cells) and primary sebaceous gland cells, stimulated by linoleic acid (LA) and dihydrotestosterone (DHT), respectively. CDCA's mechanisms were explored using transcriptomics, proteomics, and fatty acid-targeted metabolomics. In vivo validation was conducted via intradermal injection of CDCA into the sebaceous gland area of golden hamsters to assess its effect on sebaceous lipid metabolism.</p><p><strong>Results: </strong>CDCA significantly reduced intracellular lipid accumulation in both murine prostate cancer cells (RM-1) and primary sebaceous gland cells, and suppressed the expression of the androgen receptor (AR), along with the downregulation of key lipogenic enzymes (SREBF1, FASN, FADS2). Mitochondrial membrane potential was restored in CDCA-treated cells. Multi-omics analyses revealed that CDCA modulated fatty acid biosynthesis and degradation, energy metabolism, mitochondrial function, and Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) signaling. Lipidomic profiling demonstrated a shift from saturated to unsaturated fatty acid dominance after CDCA treatment. In vivo, CDCA decreased sebaceous lipid accumulation and downregulated PPAR-γ expression in golden hamsters.</p><p><strong>Conclusion: </strong>CDCA exerted multifaceted regulatory effects on lipid metabolism, hormone signaling, and mitochondrial dynamics. These effects contributed to the maintenance of sebaceous gland homeostasis and supported the development of innovative and potentially more biocompatible therapies for lipid-related disorders.</p>\",\"PeriodicalId\":18073,\"journal\":{\"name\":\"Lipids in Health and Disease\",\"volume\":\"24 1\",\"pages\":\"238\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261562/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lipids in Health and Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12944-025-02656-w\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lipids in Health and Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12944-025-02656-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Multiomics analysis revealed the regulatory role of chenodeoxycholic acid in fatty acid metabolism and lipid homeostasis.
Objective: This study aimed to investigate the regulatory role and mechanisms of chenodeoxycholic acid (CDCA) on lipid metabolism, and to evaluate its therapeutic potential in lipid metabolism-related diseases such as acne, seborrheic alopecia, and prostate cancer, with the aim of identifying safer and more sustainable treatment alternatives.
Methods: Lipid-overproduction models were established using RM-1 (murine prostate cancer cells) and primary sebaceous gland cells, stimulated by linoleic acid (LA) and dihydrotestosterone (DHT), respectively. CDCA's mechanisms were explored using transcriptomics, proteomics, and fatty acid-targeted metabolomics. In vivo validation was conducted via intradermal injection of CDCA into the sebaceous gland area of golden hamsters to assess its effect on sebaceous lipid metabolism.
Results: CDCA significantly reduced intracellular lipid accumulation in both murine prostate cancer cells (RM-1) and primary sebaceous gland cells, and suppressed the expression of the androgen receptor (AR), along with the downregulation of key lipogenic enzymes (SREBF1, FASN, FADS2). Mitochondrial membrane potential was restored in CDCA-treated cells. Multi-omics analyses revealed that CDCA modulated fatty acid biosynthesis and degradation, energy metabolism, mitochondrial function, and Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) signaling. Lipidomic profiling demonstrated a shift from saturated to unsaturated fatty acid dominance after CDCA treatment. In vivo, CDCA decreased sebaceous lipid accumulation and downregulated PPAR-γ expression in golden hamsters.
Conclusion: CDCA exerted multifaceted regulatory effects on lipid metabolism, hormone signaling, and mitochondrial dynamics. These effects contributed to the maintenance of sebaceous gland homeostasis and supported the development of innovative and potentially more biocompatible therapies for lipid-related disorders.
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.
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