Sex matters in liver fat regulation.
Sex matters in liver fat regulation.
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性别对肝脏脂肪调节很重要。
DOI：
10.1126/science.ade7614
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Kineman,RhondaD
中科院分区：
文献类型：
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作者：
Waxman,DavidJ;Kineman,RhondaD
在人类和啮齿类动物中，男性比（绝经前）女性更容易发生饮食诱导的肝脏脂肪蓄积（脂肪变性）和进展为非酒精性脂肪肝病（NAFLD）、肝纤维化和肝细胞癌。肝脏基因表达的性别特异性差异主要由垂体生长激素（GH）分泌的性别依赖性时间模式控制。然而，GH调节基因表达的性别差异和肝脏代谢疾病的性别差异之间的联系，这往往归因于性腺类固醇的直接影响，知之甚少。在本期的第290页，Nikkanenet al.show报道，与雌性小鼠相比，B细胞淋巴瘤6（BCL 6），一种性别依赖性、GH调节的肝脏转录因子，使雄性小鼠对高脂饮食诱导的NAFLD的易感性增加。然而，BCL6也提供了一个意想不到的好处，即在细菌感染后增加男性的存活率，这表明了进化的权衡。
Males are more susceptible than (premenopausal) females to diet-induced hepatic fat accumulation (steatosis) and progression to nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and hepatocellular carcinoma, in both humans and rodents . Sex-specific differences in liver gene expression are primarily controlled by the sex-dependent temporal patterns of pituitary growth hormone (GH) secretion . However, the links between sex differences in GH-regulated gene expression and sex differences in liver metabolic disease, which are often ascribed to direct effects of gonadal steroids, are poorly understood. On page 290 of this issue, Nikkanenet al.show that B cell lymphoma 6 (BCL6), a sex-dependent, GH-regulated hepatic transcription factor, drives the increased susceptibility of male mice to high-fat diet–induced NAFLD, compared to female mice. However, BCL6 also provides an unexpected benefit in the form of increased male survival after bacterial infection, suggesting an evolutionary trade-off.