Taghibiglou Changiz, Martin Henry G S, Rose Jacqueline K, Ivanova Nadia, Lin Conny H C, Lau H Lee, Rai Susan, Wang Yu Tian, Rankin Catharine H
Department of Medicine, UBC, Canada; Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5.
FEBS Lett. 2009 Feb 18;583(4):831-4. doi: 10.1016/j.febslet.2009.01.045. Epub 2009 Jan 31.
Epidemiological evidence suggests a link between chronic oxygen starvation and fat accumulation/obesity, however the underlying mechanism remains unclear. Using Caenorhabditis elegans we found extended oxygen deprivation resulted in activation of SBP-1, the worm homologue of SREBP1, a transcription factor important in maintaining lipid homeostasis. SBP-1 knockdown prevented hypoxia-induced fat accumulation and the associated increase in worm width/length ratio, demonstrating that SBP-1/SREBP1 plays an essential role in hypoxia-induced lipid accumulation and body shape alteration. This study provides the first evidence suggesting that activation of SREBP1 may be a critical pathogenic factor contributing to chronic hypoxia associated excessive fat accumulation/obesity in humans.
流行病学证据表明慢性缺氧与脂肪堆积/肥胖之间存在联系，然而其潜在机制仍不清楚。利用秀丽隐杆线虫，我们发现长时间缺氧会导致SBP-1（SREBP1的线虫同源物，一种在维持脂质稳态中起重要作用的转录因子）的激活。敲低SBP-1可防止缺氧诱导的脂肪堆积以及线虫宽度/长度比的相关增加，这表明SBP-1/SREBP1在缺氧诱导的脂质堆积和体型改变中起关键作用。这项研究首次提供证据表明，SREBP1的激活可能是导致人类慢性缺氧相关的过度脂肪堆积/肥胖的关键致病因素。
