High-fat diet alters retinal lipid composition and gene expression networks in mice
Abstract Background High-fat diet (HFD) was suggested to be associated with several retinal diseases, including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). Nevertheless, our understanding of the mechanisms governing retinal lipid metabolic homeostasis remains lim...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s12915-025-02212-z |
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| author | Rong Zou Jinrui Cai Tianyu Chen Wenhui Mo Hao Qian Xianjun Zhu Lin Zhang |
| author_facet | Rong Zou Jinrui Cai Tianyu Chen Wenhui Mo Hao Qian Xianjun Zhu Lin Zhang |
| author_sort | Rong Zou |
| collection | DOAJ |
| description | Abstract Background High-fat diet (HFD) was suggested to be associated with several retinal diseases, including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). Nevertheless, our understanding of the mechanisms governing retinal lipid metabolic homeostasis remains limited, with little attention focused on the influence of HFD on different retinal cell types. To address this gap, we established a high-fat model using mice fed with HFD for a duration of 6 months. Then, we conducted a comparative analysis of the retinal lipidome and proteome between normal diet (ND) and HFD-fed mice to explore the impacts of HFD on retinal lipid metabolism and gene expression network. Furthermore, we also investigated the impacts of HFD on retina in single-cell resolution by single-cell transcriptome sequencing. Results We found that a long-term HFD significantly altered the lipid composition of the retina, with a dramatically elevated cholesterylesters (CE), phosphatidylcholine (PC), and phosphatidylglycerol (PG) level and a decreased eicosanoid level. Proteomic analysis revealed that the primary bile acid biosynthesis pathway was over-activated in HFD retinas. By using single-cell transcriptome analysis, we identified different regulation of gene expression in MG and rod cells in a high-fat environment, whereas the previously identified activation of the bile acid synthesis pathway was predominantly found in MG cells, and may be regulated by alternative pathways of bile acid synthesis, suggesting the critical roles of MG cells in retinal lipid metabolism. Conclusions Taken together, by multi-omics studies, we unveiled that HFD leading to the development of retinal diseases may be regulated by alternative pathways of bile acid synthesis, and our study will shed light on the treatment of these diseases. |
| format | Article |
| id | doaj-art-5037d28512c6424aa8b1511cf73ddac1 |
| institution | OA Journals |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-5037d28512c6424aa8b1511cf73ddac12025-08-20T02:17:58ZengBMCBMC Biology1741-70072025-04-0123111610.1186/s12915-025-02212-zHigh-fat diet alters retinal lipid composition and gene expression networks in miceRong Zou0Jinrui Cai1Tianyu Chen2Wenhui Mo3Hao Qian4Xianjun Zhu5Lin Zhang6The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaAbstract Background High-fat diet (HFD) was suggested to be associated with several retinal diseases, including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). Nevertheless, our understanding of the mechanisms governing retinal lipid metabolic homeostasis remains limited, with little attention focused on the influence of HFD on different retinal cell types. To address this gap, we established a high-fat model using mice fed with HFD for a duration of 6 months. Then, we conducted a comparative analysis of the retinal lipidome and proteome between normal diet (ND) and HFD-fed mice to explore the impacts of HFD on retinal lipid metabolism and gene expression network. Furthermore, we also investigated the impacts of HFD on retina in single-cell resolution by single-cell transcriptome sequencing. Results We found that a long-term HFD significantly altered the lipid composition of the retina, with a dramatically elevated cholesterylesters (CE), phosphatidylcholine (PC), and phosphatidylglycerol (PG) level and a decreased eicosanoid level. Proteomic analysis revealed that the primary bile acid biosynthesis pathway was over-activated in HFD retinas. By using single-cell transcriptome analysis, we identified different regulation of gene expression in MG and rod cells in a high-fat environment, whereas the previously identified activation of the bile acid synthesis pathway was predominantly found in MG cells, and may be regulated by alternative pathways of bile acid synthesis, suggesting the critical roles of MG cells in retinal lipid metabolism. Conclusions Taken together, by multi-omics studies, we unveiled that HFD leading to the development of retinal diseases may be regulated by alternative pathways of bile acid synthesis, and our study will shed light on the treatment of these diseases.https://doi.org/10.1186/s12915-025-02212-zHFDMetabolic homeostasisRetinaCholesterol |
| spellingShingle | Rong Zou Jinrui Cai Tianyu Chen Wenhui Mo Hao Qian Xianjun Zhu Lin Zhang High-fat diet alters retinal lipid composition and gene expression networks in mice BMC Biology HFD Metabolic homeostasis Retina Cholesterol |
| title | High-fat diet alters retinal lipid composition and gene expression networks in mice |
| title_full | High-fat diet alters retinal lipid composition and gene expression networks in mice |
| title_fullStr | High-fat diet alters retinal lipid composition and gene expression networks in mice |
| title_full_unstemmed | High-fat diet alters retinal lipid composition and gene expression networks in mice |
| title_short | High-fat diet alters retinal lipid composition and gene expression networks in mice |
| title_sort | high fat diet alters retinal lipid composition and gene expression networks in mice |
| topic | HFD Metabolic homeostasis Retina Cholesterol |
| url | https://doi.org/10.1186/s12915-025-02212-z |
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