Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes
Abstract Saturated fatty acid (SFA) and unsaturated fatty acid (UFA) have distinct impacts on health. Whether SFA and UFA are differentially transported in liver remains elusive. Here, we find the secretion of UFA but not SFA esters is retarded in a male mouse hepatic endoplasmic reticulum (ER) stre...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56620-4 |
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| author | Fengwu Chen Aizhen Yang Yue Lu Yuxin Zhang Jingyu Zhang Jianan Bu Runlin Guo Yue Han Depei Wu Yi Wu |
| author_facet | Fengwu Chen Aizhen Yang Yue Lu Yuxin Zhang Jingyu Zhang Jianan Bu Runlin Guo Yue Han Depei Wu Yi Wu |
| author_sort | Fengwu Chen |
| collection | DOAJ |
| description | Abstract Saturated fatty acid (SFA) and unsaturated fatty acid (UFA) have distinct impacts on health. Whether SFA and UFA are differentially transported in liver remains elusive. Here, we find the secretion of UFA but not SFA esters is retarded in a male mouse hepatic endoplasmic reticulum (ER) stress model. Among 13 members of protein disulfide isomerase (PDI) family, only PDIA1 (PDI) deficiency leads to hepatosteatosis and hypolipidemia. In PDI-deficient male mouse liver, there is a severe accumulation but secretory blockade of UFA esters, whereas the accumulation and secretion of SFA esters remain normal. PDI catalyzes the oxidative folding of microsomal triglyceride transfer protein (MTP). In addition, PDI deficiency in hepatocytes abolishes Apolipoprotein B-100 (ApoB-100) very low-density lipoprotein (VLDL) secretion while maintaining partial ApoB-48 VLDL secretion. In summary, we find that the secretion of UFA esters is PDI-MTP indispensable, while SFA esters could be transferred out of liver via ApoB-48 VLDL through a PDI-MTP-independent pathway. |
| format | Article |
| id | doaj-art-ffbb1ec385764620aa40008e3d923065 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ffbb1ec385764620aa40008e3d9230652025-02-09T12:45:39ZengNature PortfolioNature Communications2041-17232025-02-0116111710.1038/s41467-025-56620-4Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytesFengwu Chen0Aizhen Yang1Yue Lu2Yuxin Zhang3Jingyu Zhang4Jianan Bu5Runlin Guo6Yue Han7Depei Wu8Yi Wu9National Clinical Research Center for Hematologic Diseases, Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow UniversityNational Clinical Research Center for Hematologic Diseases, Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow UniversityNational Clinical Research Center for Hematologic Diseases, Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow UniversityNational Clinical Research Center for Hematologic Diseases, Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow UniversityDepartment of Hematology, Key Laboratory of Hematology of Hebei Province, The Second Hospital of Hebei Medical UniversityNational Clinical Research Center for Hematologic Diseases, Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow UniversityNational Clinical Research Center for Hematologic Diseases, Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow UniversityNational Clinical Research Center for Hematologic Diseases, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow UniversityNational Clinical Research Center for Hematologic Diseases, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, First Affiliated Hospital of Soochow UniversityNational Clinical Research Center for Hematologic Diseases, Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow UniversityAbstract Saturated fatty acid (SFA) and unsaturated fatty acid (UFA) have distinct impacts on health. Whether SFA and UFA are differentially transported in liver remains elusive. Here, we find the secretion of UFA but not SFA esters is retarded in a male mouse hepatic endoplasmic reticulum (ER) stress model. Among 13 members of protein disulfide isomerase (PDI) family, only PDIA1 (PDI) deficiency leads to hepatosteatosis and hypolipidemia. In PDI-deficient male mouse liver, there is a severe accumulation but secretory blockade of UFA esters, whereas the accumulation and secretion of SFA esters remain normal. PDI catalyzes the oxidative folding of microsomal triglyceride transfer protein (MTP). In addition, PDI deficiency in hepatocytes abolishes Apolipoprotein B-100 (ApoB-100) very low-density lipoprotein (VLDL) secretion while maintaining partial ApoB-48 VLDL secretion. In summary, we find that the secretion of UFA esters is PDI-MTP indispensable, while SFA esters could be transferred out of liver via ApoB-48 VLDL through a PDI-MTP-independent pathway.https://doi.org/10.1038/s41467-025-56620-4 |
| spellingShingle | Fengwu Chen Aizhen Yang Yue Lu Yuxin Zhang Jingyu Zhang Jianan Bu Runlin Guo Yue Han Depei Wu Yi Wu Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes Nature Communications |
| title | Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes |
| title_full | Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes |
| title_fullStr | Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes |
| title_full_unstemmed | Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes |
| title_short | Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes |
| title_sort | differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes |
| url | https://doi.org/10.1038/s41467-025-56620-4 |
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