Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis
Apolipoprotein H (APOH) downregulation can cause hepatic steatosis and gut microbiota dysbiosis. However, the mechanism by which APOH-regulated lipid metabolism contributes to metabolic dysfunction–associated steatotic liver disease (MASLD) remains undetermined. Herein, we aim to explore the regulat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227523001566 |
| _version_ | 1827374971637202944 |
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| author | Yaming Liu Yiqun Zhao Qiusong Liu Binbin Li P. Vineeth Daniel Binbin Chen Zeyi Wu |
| author_facet | Yaming Liu Yiqun Zhao Qiusong Liu Binbin Li P. Vineeth Daniel Binbin Chen Zeyi Wu |
| author_sort | Yaming Liu |
| collection | DOAJ |
| description | Apolipoprotein H (APOH) downregulation can cause hepatic steatosis and gut microbiota dysbiosis. However, the mechanism by which APOH-regulated lipid metabolism contributes to metabolic dysfunction–associated steatotic liver disease (MASLD) remains undetermined. Herein, we aim to explore the regulatory effect of APOH, mediated through various pathways, on metabolic homeostasis and MASLD pathogenesis. We analyzed serum marker levels, liver histopathology, and cholesterol metabolism–related gene expression in global ApoH−/− C57BL/6 male mice. We used RNA sequencing and metabolomic techniques to investigate the association between liver metabolism and bacterial composition. Fifty-two differentially expressed genes were identified between ApoH−/− and WT mice. The mRNA levels of de novo lipogenesis genes were highly upregulated in ApoH−/− mice than in WT mice. Fatty acid, glycerophospholipid, sterol lipid, and triglyceride levels were elevated, while hyodeoxycholic acid levels were significantly reduced in the liver tissues of ApoH−/− mice than in those of WT mice. Microbial beta diversity was lower in ApoH−/− mice than in WT mice, and gut microbiota metabolic functions were activated in ApoH−/− mice. Moreover, ApoH transcripts were downregulated in patients with MASLD, and APOH-related differential genes were enriched in lipid metabolism. Open-source transcript-level data from human metabolic dysfunction–associated steatohepatitis livers reinforced a significant association between metabolic dysfunction–associated steatohepatitis and APOH downregulation. In conclusion, our studies demonstrated that APOH downregulation aggravates fatty liver and induces gut microbiota dysbiosis by dysregulating bile acids. Our findings offer a novel perspective on APOH-mediated lipid metabolic dysbiosis and provide a valuable framework for deciphering the role of APOH in fatty liver disease. |
| first_indexed | 2024-03-08T11:43:00Z |
| format | Article |
| id | doaj.art-f0cd3cf0969a4eb2940685007ec660f0 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-03-08T11:43:00Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-f0cd3cf0969a4eb2940685007ec660f02024-01-25T05:22:32ZengElsevierJournal of Lipid Research0022-22752024-01-01651100483Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosisYaming Liu0Yiqun Zhao1Qiusong Liu2Binbin Li3P. Vineeth Daniel4Binbin Chen5Zeyi Wu6Department of Gastroenterology and Hepatology, Xiamen University Zhongshan Hospital, Xiamen, FJ, China; Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, FJ, China; For correspondence: Yaming LiuDepartment of Gastroenterology and Hepatology, Xiamen University Zhongshan Hospital, Xiamen, FJ, China; Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, FJ, ChinaDepartment of Tumor and Vascular Interventional Radiology, Xiamen University Zhongshan Hospital, Xiamen, FJ, ChinaDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USADepartment of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, FJ, ChinaDepartment of Computer Science and Engineering, University of California, San Diego, CA, USAApolipoprotein H (APOH) downregulation can cause hepatic steatosis and gut microbiota dysbiosis. However, the mechanism by which APOH-regulated lipid metabolism contributes to metabolic dysfunction–associated steatotic liver disease (MASLD) remains undetermined. Herein, we aim to explore the regulatory effect of APOH, mediated through various pathways, on metabolic homeostasis and MASLD pathogenesis. We analyzed serum marker levels, liver histopathology, and cholesterol metabolism–related gene expression in global ApoH−/− C57BL/6 male mice. We used RNA sequencing and metabolomic techniques to investigate the association between liver metabolism and bacterial composition. Fifty-two differentially expressed genes were identified between ApoH−/− and WT mice. The mRNA levels of de novo lipogenesis genes were highly upregulated in ApoH−/− mice than in WT mice. Fatty acid, glycerophospholipid, sterol lipid, and triglyceride levels were elevated, while hyodeoxycholic acid levels were significantly reduced in the liver tissues of ApoH−/− mice than in those of WT mice. Microbial beta diversity was lower in ApoH−/− mice than in WT mice, and gut microbiota metabolic functions were activated in ApoH−/− mice. Moreover, ApoH transcripts were downregulated in patients with MASLD, and APOH-related differential genes were enriched in lipid metabolism. Open-source transcript-level data from human metabolic dysfunction–associated steatohepatitis livers reinforced a significant association between metabolic dysfunction–associated steatohepatitis and APOH downregulation. In conclusion, our studies demonstrated that APOH downregulation aggravates fatty liver and induces gut microbiota dysbiosis by dysregulating bile acids. Our findings offer a novel perspective on APOH-mediated lipid metabolic dysbiosis and provide a valuable framework for deciphering the role of APOH in fatty liver disease.http://www.sciencedirect.com/science/article/pii/S0022227523001566apolipoprotein Hcholesterol/metabolismbile acids and saltstriglyceridesde novo lipogenesishepatocyte |
| spellingShingle | Yaming Liu Yiqun Zhao Qiusong Liu Binbin Li P. Vineeth Daniel Binbin Chen Zeyi Wu Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis Journal of Lipid Research apolipoprotein H cholesterol/metabolism bile acids and salts triglycerides de novo lipogenesis hepatocyte |
| title | Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis |
| title_full | Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis |
| title_fullStr | Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis |
| title_full_unstemmed | Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis |
| title_short | Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis |
| title_sort | effects of apolipoprotein h downregulation on lipid metabolism fatty liver disease and gut microbiota dysbiosis |
| topic | apolipoprotein H cholesterol/metabolism bile acids and salts triglycerides de novo lipogenesis hepatocyte |
| url | http://www.sciencedirect.com/science/article/pii/S0022227523001566 |
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