Morán-Costoya Andrea, Proenza Ana M, Gianotti Magdalena, Lladó Isabel, Valle Adamo
Energy Metabolism and Nutrition Group, Department of Fundamental Biology and Health Sciences, Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, Palma, Spain.
Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
Antioxid Redox Signal. 2021 Sep 20;35(9):753-774. doi: 10.1089/ars.2021.0044. Epub 2021 May 4.
Nonalcoholic fatty liver disease (NAFLD) is a hepatic and systemic disorder with a complex multifactorial pathogenesis. Owing to the rising incidence of obesity and diabetes mellitus, the prevalence of NAFLD and its impact on global health care are expected to increase in the future. Differences in NAFLD exist between males and females, and among females depending on their reproductive status. Clinical and preclinical data show that females in the fertile age are more protected against NAFLD, and studies in postmenopausal women and ovariectomized animal models support a protective role for estrogens. An efficient crosstalk between the liver and adipose tissue is necessary to regulate lipid and glucose metabolism, protecting the liver from steatosis and insulin resistance contributing to NALFD. New advances in the knowledge of sexual dimorphism in liver and adipose tissue are providing interesting clues about the sex differences in NAFLD pathogenesis that could inspire new therapeutic strategies. Sex hormones influence key master regulators of lipid metabolism and oxidative stress in liver and adipose tissue. All these sex-biased metabolic adjustments shape the crosstalk between liver and adipose tissue, contributing to the higher protection of females to NAFLD. The development of novel drugs based on the protective action of estrogens, but without its feminizing or undesired side effects, might provide new therapeutic strategies for the management of NAFLD. . 35, 753-774.
非酒精性脂肪性肝病（NAFLD）是一种具有复杂多因素发病机制的肝脏和全身性疾病。由于肥胖症和糖尿病的发病率不断上升，预计NAFLD的患病率及其对全球医疗保健的影响在未来将会增加。NAFLD在男性和女性之间存在差异，在女性中也因生殖状态而异。临床和临床前数据表明，育龄期女性对NAFLD的抵抗力更强，对绝经后女性和去卵巢动物模型的研究支持雌激素具有保护作用。肝脏与脂肪组织之间有效的相互作用对于调节脂质和葡萄糖代谢至关重要，可保护肝脏免受脂肪变性和胰岛素抵抗的影响，而这两者都会导致NAFLD。肝脏和脂肪组织中性别二态性知识的新进展为NAFLD发病机制中的性别差异提供了有趣的线索，这可能会激发新的治疗策略。性激素会影响肝脏和脂肪组织中脂质代谢和氧化应激的关键主要调节因子。所有这些性别偏向的代谢调节塑造了肝脏与脂肪组织之间的相互作用，从而使女性对NAFLD具有更高的抵抗力。基于雌激素的保护作用开发新型药物，但没有其女性化或不良副作用，可能为NAFLD的管理提供新的治疗策略。. 35, 753 - 774。
