Meyer Jana, Teixeira Ana Mendes, Richter Sandy, Larner Dean P, Syed Asifuddin, Klöting Nora, Matz-Soja Madlen, Gaul Susanne, Barnikol-Oettler Anja, Kiess Wieland, Le Duc Diana, Penke Melanie, Garten Antje
Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig University, Leipzig, Germany.
Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Front Endocrinol (Lausanne). 2025 Mar 14;16:1567573. doi: 10.3389/fendo.2025.1567573. eCollection 2025.
Males suffer more often from profibrotic changes in liver than females. The underlying mechanism for this sex difference in the prevalence and manifestation of Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) is not yet completely known. We studied male and female mice that were induced to develop MASLD by consuming a "fast food" diet (FFD) and assessed metabolic phenotype as well as liver histology and compared them with mice fed with a matched control diet (CD). Our aim was to check for sex-specific differences in MASLD development in a mouse model of diet-induced profibrotic changes in the liver. Our results demonstrate a clear difference in body weight, fat distribution and changes in liver tissue for male and female mice fed with FFD. We found that female mice stored lipids mainly in subcutaneous and visceral adipose tissue while males increased ectopic lipid accumulation in the liver which resulted in hepatomegaly and increased () and () expression concomitant to fibrosis development. This was absent in female mice. Analysis of estrogen receptor -α and -β expression revealed an upregulation of in livers of male FFD-fed mice whereas in female liver tissue a higher expression in could be observed. This study supports and as potential targets to reverse negative effects of diet-induced profibrotic changes in the liver.
男性比女性更容易出现肝脏的促纤维化改变。代谢功能障碍相关脂肪性肝病（MASLD）患病率和表现存在性别差异的潜在机制尚未完全明确。我们研究了通过食用“快餐”饮食（FFD）诱导发生MASLD的雄性和雌性小鼠，评估了它们的代谢表型以及肝脏组织学，并将其与喂食匹配对照饮食（CD）的小鼠进行比较。我们的目的是在饮食诱导肝脏促纤维化改变的小鼠模型中检测MASLD发展过程中的性别特异性差异。我们的结果表明，喂食FFD的雄性和雌性小鼠在体重、脂肪分布和肝脏组织变化方面存在明显差异。我们发现，雌性小鼠主要将脂质储存在皮下和内脏脂肪组织中，而雄性小鼠肝脏中的异位脂质积累增加，导致肝脏肿大，并伴随纤维化发展增加了（）和（）的表达。雌性小鼠则没有这种情况。对雌激素受体-α和-β表达的分析显示，喂食FFD的雄性小鼠肝脏中（）上调，而在雌性肝脏组织中可观察到（）表达更高。本研究支持（）和（）作为逆转饮食诱导的肝脏促纤维化改变负面影响的潜在靶点。
