| Autor: |
Xinlu Ji, Hongli Yin, Tianwei Gu, Hao Xu, Da Fang, Kai Wang, Haixiang Sun, Sai Tian, Tianyu Wu, Yuanyuan Nie, Pengzi Zhang, Yan Bi |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 43, Iss 7, Pp 114465- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114465 |
| Popis: |
Summary: The pituitary is the central endocrine gland with effects on metabolic dysfunction-associated steatotic liver disease (MASLD). However, it is not clear whether the pituitary responds to free fatty acid (FFA) toxicity, thus dysregulating hepatic lipid metabolism. Here, we demonstrate that decreased prolactin (PRL) levels are involved in the association between FFA and MASLD based on a liver biospecimen-based cohort. Moreover, overloaded FFAs decrease serum PRL levels, thus promoting liver steatosis in mice with both dynamic diet intervention and stereotactic pituitary FFA injection. Mechanistic studies show that excessive FFA sensing in pituitary lactotrophs inhibits the synthesis and secretion of PRL in a cell-autonomous manner. Notably, inhibiting excessive lipid uptake using pituitary stereotaxic virus injection or a specific drug delivery system effectively ameliorates hepatic lipid accumulation by improving PRL levels. Targeted inhibition of pituitary FFA sensing may be a potential therapeutic target for liver steatosis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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