Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Precision Pathology of Neoplasia Research Group, Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Front Endocrinol (Lausanne). 2024 Sep 16;15:1392866. doi: 10.3389/fendo.2024.1392866. eCollection 2024.
Obesity is associated with insulin resistance (IR) and metabolic dysfunction-associated steatotic liver disease (MASLD). Genistein, an isoflavone, is a promising natural compound for preventing and treating obesity and metabolic dysfunctions. We aimed to investigate the sex-specific protective effects of genistein on obesity, IR, and MASLD in a murine model of sex hormone deprivation with diet-induced obesity (DIO), mimicking postmenopausal women or aging men with metabolic syndrome.
Gonadectomized and sham-operated C57BL/6NJcl mice were fed a high-fat high-sucrose diet for 4 weeks to induce obesity (7 mice per group). In gonadectomized mice, genistein (16 mg/kg/day) or vehicle (7.5% dimethyl sulfoxide) was orally administered for 45 days. We assessed glucose homeostasis parameters, hepatic histopathology, and hepatic gene expression to investigate the effects of gonadectomy and genistein treatment.
Gonadectomy exacerbated adiposity in both sexes. Ovariectomy diminished the protective effects of female gonadal hormones on the homeostatic model assessment for insulin resistance (HOMA-IR), serum alanine transaminase levels, hepatic steatosis score, and the expression of hepatic genes associated with MASLD progression and IR, such as , , , , , , and . Genistein treatment in gonadectomized mice significantly reduced body weight gain and the hepatic steatosis score in both sexes. However, genistein treatment significantly attenuated HOMA-IR and the expression of the hepatic genes only in female mice.
Genistein treatment mitigates DIO-related MASLD in both male and female gonadectomized mice. Regarding hepatic gene expression associated with MASLD and IR, the beneficial effect of genistein was significantly evident only in female mice. This study suggests a potential alternative application of genistein in individuals with obesity and sex hormone deprivation, yet pending clinical trials.
肥胖与胰岛素抵抗（IR）和代谢功能障碍相关的脂肪性肝病（MASLD）有关。染料木黄酮，一种异黄酮，是预防和治疗肥胖和代谢功能障碍的有前途的天然化合物。我们旨在研究染料木黄酮对去势和饮食诱导肥胖（DIO）雄性激素剥夺肥胖模型中肥胖、IR 和 MASLD 的性别特异性保护作用，该模型模拟了具有代谢综合征的绝经后妇女或衰老男性。
对 C57BL/6NJcl 雌雄去势和假手术小鼠进行高脂高蔗糖饮食喂养 4 周以诱导肥胖（每组 7 只）。在去势小鼠中，给予染料木黄酮（16mg/kg/天）或载体（7.5%二甲基亚砜）口服 45 天。我们评估葡萄糖稳态参数、肝组织病理学和肝基因表达，以研究去势和染料木黄酮治疗的影响。
去势加剧了两性肥胖。卵巢切除术减弱了女性性腺激素对胰岛素抵抗稳态模型评估（HOMA-IR）、血清丙氨酸转氨酶水平、肝脂肪变性评分以及与 MASLD 进展和 IR 相关的肝基因表达的保护作用，如 、 、 、 、 、 和 。去势小鼠中染料木黄酮治疗显著降低了两性的体重增加和肝脂肪变性评分。然而，染料木黄酮治疗仅在雌性小鼠中显著降低了 HOMA-IR 和肝基因表达。
染料木黄酮治疗减轻了两性去势小鼠的 DIO 相关 MASLD。关于与 MASLD 和 IR 相关的肝基因表达，染料木黄酮的有益作用仅在雌性小鼠中明显。这项研究表明，染料木黄酮在肥胖和性激素剥夺个体中具有潜在的应用前景，但需要进行临床试验。
