饮食中的果糖通过微生物衍生的酸盐促进肝脂生
Steven Zhao1,2,3, Cholsoon Jang4, Joyce Liu1,2,5
1Department of Cancer Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Nature
|March 28, 2020
概括
饮食中的果糖通过两种途径驱动肝脏脂肪的产生:直接转化到肝细胞和微生物酸盐. 抑制微生物酸盐的产生可显著降低果糖诱导的脂肪酸合成.
科学领域:
- 代谢疾病研究
- 营养科学
- 肝病学
背景情况:
- 果糖消费与肥胖和脂肪肝疾病有关.
- 果糖的摄入促进了肝脏的新脂肪生成 (脂肪合成).
- 从果糖到肝脏脂肪积累的确切途径尚不清楚.
研究的目的:
- 阐明连接饮食中的果糖到肝脏乙-CoA和脂质合成的代谢途径.
- 研究ATP酸酶 (ACLY) 和肠道微生物在果糖代谢中的作用.
主要方法:
- 在小鼠体内同位素追踪.
- 肝脏特异性基因删除 (Acly).
- 肠道微生物减少和肝脏ACSS2沉默.
主要成果:
- 肝脏特异性的Acly删除没有阻止果糖诱导的脂质生成.
- 肠道微生物群将果糖转化为酸盐,独立于ACLY提供酸盐.
- 微生物群的消耗或ACSS2沉默抑制了果糖转化为肝脏的乙CoA和脂肪酸.
- 渐进的果糖摄入包括肝细胞酸盐分裂和微生物酸盐.
- 果糖可以独立于乙-CoA代谢来激活脂肪基因表达.
结论:
- 肝脏脂肪生成由双重机制调节,其中包括肝细胞果分和微生物酸盐.
- 微生物酸盐是从饮食中的果糖中获得脂质性酸盐的重要来源.
- 了解这些途径为代谢疾病的治疗提供了新的目标.
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