Personalized Diagnostics and Therapeutics, Department of Bioengineering Technologies, Technical Medical Centre, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
University of Edinburgh Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh BioQuarter, Edinburgh, UK.
Trends Pharmacol Sci. 2024 Jul;45(7):614-627. doi: 10.1016/j.tips.2024.05.004. Epub 2024 Jun 8.
Growing evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) is significantly higher in men versus women. Increased prevalence is observed in postmenopausal women, suggesting that age and sex (hormones) influence MASLD development and progression. Molecular data further reveal that sex regulates the innate immune responses with an essential role in MASLD progression. To date, there has been limited focus on the role of innate immune sexual dimorphism in MASLD, and differences between men and women are not considered in the current drug discovery landscape. In this review, we summarize the sex disparities and innate immune sexual dimorphism in MASLD pathogenesis. We further highlight the importance of harnessing sexual dimorphism in identifying therapeutic targets, developing pharmacological therapies, and designing (pre-) clinical studies for the personalized treatment for MASLD.
越来越多的证据表明，男性代谢功能相关脂肪性肝病（MASLD）的发病率明显高于女性。绝经后妇女的发病率增加，表明年龄和性别（激素）影响 MASLD 的发生和发展。分子数据进一步表明，性别调节先天免疫反应，在 MASLD 进展中起重要作用。迄今为止，人们对先天免疫性别二态性在 MASLD 中的作用关注有限，并且在当前的药物发现领域中，并未考虑男性和女性之间的差异。在这篇综述中，我们总结了 MASLD 发病机制中的性别差异和先天免疫性别二态性。我们还强调了利用性别二态性来确定治疗靶点、开发药物治疗以及设计（前）临床试验以实现 MASLD 的个体化治疗的重要性。
