1. Excessive free fatty acid sensing in pituitary lactotrophs elicits steatotic liver disease by decreasing prolactin levels.
- Author
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Ji X, Yin H, Gu T, Xu H, Fang D, Wang K, Sun H, Tian S, Wu T, Nie Y, Zhang P, and Bi Y
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Humans, Male, Lipid Metabolism, Liver metabolism, Prolactin metabolism, Prolactin blood, Fatty Acids, Nonesterified blood, Fatty Acids, Nonesterified metabolism, Fatty Liver metabolism, Fatty Liver pathology, Lactotrophs metabolism, Lactotrophs drug effects
- Abstract
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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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