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  3. Excessive free fatty acid sensing in pituitary lactotrophs elicits steatotic liver disease by decreasing prolactin levels

Excessive free fatty acid sensing in pituitary lactotrophs elicits steatotic liver disease by decreasing prolactin levels

  • Cell Rep. 2024 Jul 23;43(7):114465. doi: 10.1016/j.celrep.2024.114465.
Xinlu Ji 1,  Hongli Yin 1,  Tianwei Gu 1,  Hao Xu 1,  Da Fang 1,  Kai Wang 1,  Haixiang Sun 1,  Sai Tian 1,  Tianyu Wu 1,  Yuanyuan Nie 1,  Pengzi Zhang 2,  Yan Bi 3
Affiliations

Affiliations

  • 1 Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China.
  • 2 Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China. Electronic address: zhang_pengzi@163.com.
  • 3 Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China. Electronic address: biyan@nju.edu.cn.
PMID: 38985678 DOI: 10.1016/j.celrep.2024.114465
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.

Keywords

CP: Metabolism; free fatty acids; metabolic dysfunction-associated steatotic liver disease; metabolite sensing; prolactin.

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