肝蛋白激酶Cbeta的缺乏减轻了晚期出现的肥胖症
Yaoling Shu1, Nikhil Gumma1, Faizule Hassan1
1Department of Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
The Journal of biological chemistry
|June 14, 2023
概括
衰老会增加肝脏蛋白激酶Cbeta (PKCβ),导致肥胖. 阻断肝细胞PKCβ增加能量消耗,并对抗与年龄相关的体重增加,提供新的治疗点.
科学领域:
- 代谢生理学 代谢生理学
- 分子生物学分子生物学
- 衰老的研究研究.
背景情况:
- 衰老与身体脂肪增加和肝功能下降有关.
- 与年龄相关的代谢功能障碍的分子基础仍然不清楚.
研究的目的:
- 调查肝脏蛋白激酶Cbeta (PKCβ) 在与年龄相关的肥胖症中的作用.
- 探索在衰老过程中准PKCβ对代谢健康的潜力.
主要方法:
- 使用了具有肝细胞特异性PKCβ缺乏症 (PKCβHep-/-) 的转基因小鼠和对照 littermates (PKCβfl/fl).
- 向老年小鼠提供高脂肪饮食.
- 评估了棕色脂肪组织 (BAT) 的能量消耗,氧气消耗,二氧化碳产生和热原基因表达.
- 分析了肌肉纤维类型和线粒体功能.
主要成果:
- 衰老增加了肝脏PKCβ的表达.
- 与对照组相比,PKCβHep-/-小鼠在高脂肪饮食下显示肥胖程度降低.
- 由于PKCβ缺乏,通过β3-上腺素信号增强了能量消耗,增加了氧气消耗和二氧化碳的产生.
- 在BAT中的热生成基因表达和肌肉中的氧化能力在PKCβHep-/-小鼠中得到改善.
- 肝脏特异性PKCβ过度表达抵消了对BAT热生成的有益影响.
结论:
- 肝脏PKCβ诱导是与年龄相关的代谢下降和肥胖的一个关键因素.
- 准肝细胞PKCβ可以增强热生成并改善能量平衡.
- 研究结果表明,通过调节热生成,可以采取治疗策略来对抗因衰老引起的肥胖.
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