Publications
Detailed Information
Metformin-induced TTP mediates communication between Kupffer cells and hepatocytes to alleviate hepatic steatosis by regulating lipophagy and necroptosis
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Jeongmin | - |
dc.contributor.author | Rah, So-Young | - |
dc.contributor.author | An, Hyeong Seok | - |
dc.contributor.author | Lee, Jong Youl | - |
dc.contributor.author | Roh, Gu Seob | - |
dc.contributor.author | Ryter, Stefan W. | - |
dc.contributor.author | Park, Jeong Woo | - |
dc.contributor.author | Yang, Chae Ha | - |
dc.contributor.author | Surh, Young-Joon | - |
dc.contributor.author | Kim, Uh-Hyun | - |
dc.contributor.author | Chung, Hun Taeg | - |
dc.contributor.author | Joe, Yeonsoo | - |
dc.date.accessioned | 2023-05-10T01:21:45Z | - |
dc.date.available | 2023-05-10T01:21:45Z | - |
dc.date.created | 2023-04-21 | - |
dc.date.created | 2023-04-21 | - |
dc.date.created | 2023-04-21 | - |
dc.date.created | 2023-04-21 | - |
dc.date.created | 2023-04-21 | - |
dc.date.issued | 2023-04 | - |
dc.identifier.citation | Metabolism: Clinical and Experimental, Vol.141, p. 155516 | - |
dc.identifier.issn | 0026-0495 | - |
dc.identifier.uri | https://hdl.handle.net/10371/192243 | - |
dc.description.abstract | Objective: Emerging evidence suggests that crosstalk between Kupffer cells (KCs) and hepatocytes protects against non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms that lead to the reduction of steatosis in NAFLD remain obscure. Methods: Ttp+/+ and Ttp−/− mice were fed with a high-fat diet. Hepatic steatosis was analyzed by Nile Red staining and measurement of inflammatory cytokines. Lipid accumulation and cell death were evaluated in co-culture systems with primary hepatocytes and KCs derived from either Ttp+/+ or Ttp−/− mice. Results: Tristetraprolin (TTP), an mRNA binding protein, was essential for the protective effects of metformin in NAFLD. Metformin activated TTP via the AMPK-Sirt1 pathway in hepatocytes and KCs. TTP inhibited TNF-α production in KCs, which in turn decreased hepatocyte necroptosis. Downregulation of Rheb expression by TTP promoted hepatocyte lipophagy via mTORC1 inhibition and increased nuclear translocation of transcription factor-EB (TFEB). Consistently, TTP-deficient NAFLD mice failed to respond to metformin with respect to alleviation of hepatic steatosis, protection of hepatocyte necroptosis, or induction of lipophagy. Conclusions: TTP, which is essential for the protective effects of metformin, may represent a novel primary therapeutic target in NAFLD. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier BV | - |
dc.title | Metformin-induced TTP mediates communication between Kupffer cells and hepatocytes to alleviate hepatic steatosis by regulating lipophagy and necroptosis | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.metabol.2023.155516 | - |
dc.citation.journaltitle | Metabolism: Clinical and Experimental | - |
dc.identifier.wosid | 001141860700001 | - |
dc.identifier.scopusid | 2-s2.0-85147704716 | - |
dc.citation.startpage | 155516 | - |
dc.citation.volume | 141 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Surh, Young-Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ACTIVATED PROTEIN-KINASE | - |
dc.subject.keywordPlus | FATTY LIVER-DISEASE | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | MTORC1 | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | INDUCTION | - |
dc.subject.keywordPlus | ADIPOCYTES | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | PROMOTES | - |
dc.subject.keywordAuthor | Hepatocytes | - |
dc.subject.keywordAuthor | Kupffer cells | - |
dc.subject.keywordAuthor | Lipophagy | - |
dc.subject.keywordAuthor | Metformin | - |
dc.subject.keywordAuthor | Necroptosis | - |
dc.subject.keywordAuthor | Non-alcoholic fatty liver disease | - |
dc.subject.keywordAuthor | Sirt1 | - |
dc.subject.keywordAuthor | Tristetraprolin | - |
- Appears in Collections:
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.