Essential role of SBP-1 activation in oxygen deprivation induced lipid accumulation and increase in body width/length ratio in Caenorhabditis elegans

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.