Hepatology international · 2026
Prolactin acts on proopiomelanocortin neurons to regulate hepatic lipid metabolism.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhu Ye, Wu Kexin, Wu Tianyu, Fang Da, Zhang Pengzi, Wang Jin, Bi Yan
Аннотация
OBJECTIVE: To elucidate the central mechanism of pituitary-derived prolactin (PRL) in hepatic lipid homeostasis and identify therapeutic targets for metabolic dysfunction-associated fatty liver disease (MASLD).
METHODS: High-fat diet (HFD)-fed mice induced MASLD. PRL⁻/⁻ mice, POMC neuron-specific PRL receptor (PRLR) conditional knockout mice, AAV-mediated PRLR knockdown, and central/peripheral PRL administration were used to explore PRL's central regulatory role. Metabolic phenotyping, histological/biochemical assays, immunofluorescence, electrophysiology, RNA-seq, 6-OHDA-induced sympathetic denervation, and primary hepatocyte experiments were performed to evaluate phenotypes, neuronal activity and underlying mechanisms.
RESULTS: PRL deficiency exacerbated HFD-induced hepatic lipid deposition, and central intracerebroventricular PRL alleviated hepatic steatosis in HFD-fed PRL⁻/⁻ and wild-type mice more rapidly than peripheral intraperitoneal PRL. PRLR was highly expressed in hypothalamic arcuate nucleus POMC neurons, which PRL selectively activated by enhancing neuronal excitability. POMC-specific PRLR knockout abrogated PRL's anti-steatotic effects and aggravated HFD-induced hepatic lipid accumulation. Mechanistically, central PRL enhanced hepatic sympathetic outflow to suppress de novo lipogenesis via the FASN pathway.
CONCLUSION: PRL acts on hypothalamic POMC neurons to enhance hepatic sympathetic activity, suppressing FASN-mediated lipogenesis and maintaining lipid homeostasis. This novel PRL-driven brain-liver circuit highlights central PRL signaling as a promising MASLD therapeutic target.
METHODS: High-fat diet (HFD)-fed mice induced MASLD. PRL⁻/⁻ mice, POMC neuron-specific PRL receptor (PRLR) conditional knockout mice, AAV-mediated PRLR knockdown, and central/peripheral PRL administration were used to explore PRL's central regulatory role. Metabolic phenotyping, histological/biochemical assays, immunofluorescence, electrophysiology, RNA-seq, 6-OHDA-induced sympathetic denervation, and primary hepatocyte experiments were performed to evaluate phenotypes, neuronal activity and underlying mechanisms.
RESULTS: PRL deficiency exacerbated HFD-induced hepatic lipid deposition, and central intracerebroventricular PRL alleviated hepatic steatosis in HFD-fed PRL⁻/⁻ and wild-type mice more rapidly than peripheral intraperitoneal PRL. PRLR was highly expressed in hypothalamic arcuate nucleus POMC neurons, which PRL selectively activated by enhancing neuronal excitability. POMC-specific PRLR knockout abrogated PRL's anti-steatotic effects and aggravated HFD-induced hepatic lipid accumulation. Mechanistically, central PRL enhanced hepatic sympathetic outflow to suppress de novo lipogenesis via the FASN pathway.
CONCLUSION: PRL acts on hypothalamic POMC neurons to enhance hepatic sympathetic activity, suppressing FASN-mediated lipogenesis and maintaining lipid homeostasis. This novel PRL-driven brain-liver circuit highlights central PRL signaling as a promising MASLD therapeutic target.