MASLD/MASH和2型糖尿病:是一枚硬币的两面? 从单一的PPAR到泛PPAR激动剂
Michael P Cooreman1, Luisa Vonghia2, Sven M Francque2
1Research and Development, Inventiva, Daix, France; Research and Development, Inventiva, New York, NY, USA.
Diabetes research and clinical practice
|May 2, 2024
概括
2型糖尿病和与代谢功能障碍相关的脂肪性肝病经常同时发生. 向氧酶增殖器激活受体 (PPARs) 显示出通过解决胰岛素抵抗和肝纤维化来治疗这两种疾病的希望.
科学领域:
- 代谢性疾病是一种代谢性疾病.
- 肝病学 肝病学是一种肝病学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 2型糖尿病 (T2D) 和与代谢功能障碍相关的脂肪性肝病 (MASLD) 是普遍存在的,相互关联的疾病.
- 胰岛素抵抗是T2D和MASLD进展的关键因素,导致肝损伤和纤维化.
- 过氧体增殖器激活受体 (PPARs) 是能量稳态的关键调节者,影响胰岛素信号传递,脂质代谢,炎症和纤维化.
研究的目的:
- 探索针对T2D和MASLD的PPAR的治疗潜力.
- 评估不同PPAR异型 (PPARα,PPARβ/δ,PPARγ) 在疾病发展途径中的作用.
- 评估泛PPAR激动剂在治疗MASLD和相关代谢功能障碍的疗效.
主要方法:
- 对代谢疾病中PPARs现有文献的审查.
- 分析PPARα,PPARβ/δ和PPARγ的不同和重叠的功能.
- 对T2D和MASLD中PPAR激动剂的临床试验数据的检查.
主要成果:
- 单个PPAR激动剂已被批准用于高甘油三血症 (PPARα) 和T2D (PPARγ).
- 双PPAR激动剂在MASLD的临床试验中产生了不同的结果.
- 泛PPAR激动剂,如拉尼菲布拉诺,在II期数据中显示其改善胰岛素耐药性,肝炎和纤维化的潜力.
结论:
- 对于MASLD和T2D的复杂生物学,PPARs代表了一个统一的治疗标.
- 针对所有三种PPAR异型,提供了一种全面的方法来解决胰岛素耐药性,炎症和纤维化.
- 对泛PPAR激动剂的进一步研究对于管理这些相互关联的代谢和肝脏疾病是有必要的.
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