Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis.
Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis.
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甲酰肽受体2决定非酒精性脂肪性肝病和脂肪性肝炎进展的性别特异性差异
DOI：
10.1038/s41467-022-28138-6
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发表时间：
2022-01-31
影响因子：
16.6
通讯作者：
Jung Y
中科院分区：
文献类型：
--
作者：
Lee C;Kim J;Han J;Oh D;Kim M;Jeong H;Kim TJ;Kim SW;Kim JN;Seo YS;Suzuki A;Kim JH;Jung Y
非酒精性脂肪性肝病（NAFLD）是全球范围内的一个重要健康问题，并进展为非酒精性脂肪性肝炎（NASH）。尽管男性NAFLD/NASH的患病率和严重程度高于绝经前女性，但性别如何影响NAFLD/NASH病理生理仍不清楚。甲酰肽受体2（FPR 2）调节几个器官中的炎症反应;然而，其在肝脏中的作用尚不清楚。在这里，我们表明FPR 2介导对饮食诱导的NAFLD/NASH的性别特异性反应。在胆碱缺乏、L-氨基酸定义的高脂饮食（CDAHFD）喂养期间，雄性小鼠和雌性小鼠均诱导了NASH样肝损伤，但与雌性小鼠相比，雄性小鼠的肝损伤更严重。Fpr 2在雌性肝细胞和健康肝脏中的表达高于雄性，FPR 2缺失加重了CDAHFD喂养的雌性小鼠的肝损伤。雌二醇诱导Fpr 2表达，保护肝细胞和肝脏免受损伤。总之，我们的研究结果表明，FPR 2介导对饮食诱导的NAFLD/NASH的性别特异性反应，这表明NAFLD/NASH的新治疗靶点。男性非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）的患病率高于绝经前女性。在这里，作者报告说，甲酰肽受体2（FPR 2）水平受雌激素调节，FPR 2有助于雌性小鼠的NAFLD抗性。
Nonalcoholic fatty liver disease (NAFLD) is an important health concern worldwide and progresses into nonalcoholic steatohepatitis (NASH). Although prevalence and severity of NAFLD/NASH are higher in men than premenopausal women, it remains unclear how sex affects NAFLD/NASH pathophysiology. Formyl peptide receptor 2 (FPR2) modulates inflammatory responses in several organs; however, its role in the liver is unknown. Here we show that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH. NASH-like liver injury was induced in both sexes during choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) feeding, but compared with females, male mice had more severe hepatic damage. Fpr2 was more highly expressed in hepatocytes and healthy livers from females than males, and FPR2 deletion exacerbated liver damage in CDAHFD-fed female mice. Estradiol induced Fpr2 expression, which protected hepatocytes and the liver from damage. In conclusion, our results demonstrate that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH, suggesting a novel therapeutic target for NAFLD/NASH. Prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) higher in men than premenopausal women. Here the authors report that formyl peptide receptor 2 (FPR2) levels are regulated by estrogen, and that FPR2 contributes to NAFLD resistance in female mice.
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影响因子：
13.5
作者：
Fujita, Koji;Nozaki, Yuichi;Nakajima, Atsushi
通讯作者：
Nakajima, Atsushi
影响因子：
25.7
作者：
Garcia-Monzon, Carmelo;Lo Iacono, Oreste;Martin-Sanz, Paloma
通讯作者：
Martin-Sanz, Paloma
影响因子：
16.6
作者：
Hyun J;Wang S;Kim J;Rao KM;Park SY;Chung I;Ha CS;Kim SW;Yun YH;Jung Y
通讯作者：
Jung Y
影响因子：
3.9
作者：
Alkhouri N;Carter-Kent C;Feldstein AE
通讯作者：
Feldstein AE
影响因子：
29.4
作者：
Clark, JM;Brancati, FL;Diehl, AM
通讯作者：
Diehl, AM