GDF15通过增加肌肉能量消耗来促进减肥
Dongdong Wang1,2, Logan K Townsend1,2, Geneviève J DesOrmeaux3
1Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada.
Nature
|June 28, 2023
概括
增长差异化因子15 (GDF15) 有助于在减肥期间维持能量消耗,改善非酒精性脂肪肝和胰岛素敏感性. 这提供了一种新的治疗策略,
科学领域:
- 代谢疾病研究
- 内分泌学
- 分子生物学
背景情况:
- 在非酒精性脂肪肝 (NAFLD) 和2型糖尿病中,卡路里限制有助于减肥,但由于能量消耗减少 (适应性热生成),重量增加很常见.
- 通过抑制食欲通过GFRAL受体,增长差异化因子15 (GDF15) 已显示出降低肥胖和改善动物血糖控制的潜力.
- GDF15影响能源支出的确切机制,特别是在CR期间,仍然不完全理解.
研究的目的:
- 研究GDF15在卡路里限制期间抵消适应性热生成的作用.
- 为了确定GDF15是否能增强体重减轻和改善代谢参数,而不仅仅是CR的影响.
- 阐明GDF15维持能量消耗的分子途径.
主要方法:
- 在高脂肪饮食中的动物中使用复合GDF15.
- 评估体重,食物摄入量,能量消耗和代谢标志物 (例如胰岛素敏感性,肝硬化).
- 在骨肌中研究GDF15-GFRAL信号轴,包括β-上腺素通路.
主要成果:
- 除了减少食物摄入外,GDF15治疗还抵消了通常在CR期间出现的能量消耗的补偿性减少.
- 与单独接受CR治疗的小鼠相比,接受GDF15治疗的小鼠的体重下降更大,NAFLD的减少更为显著.
- GDF15对能量消耗的有益影响取决于GFRAL-β-上腺素信号轴,该轴促进脂肪酸氧化和骨肌肉中的无效循环.
结论:
- 在卡路里限制期间,GDF15在维持能量消耗方面发挥着至关重要的作用,独立于食欲抑制.
- 通过骨肌肉作用的GDF15-GFRAL途径为对抗肥胖和代谢功能障碍提供了新的治疗点.
- 通过向GDF15-GFRAL轴,可以通过防止自适应性热生成来提高减肥干预措施的有效性.
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