Hypoxia Suppresses Fasting-Induced Lipolysis in Caenorhabditis Elegans

Oxygen is an essential molecule in the regulation of energy homeostasis. Particularly, oxygen is required for beta‐oxidation and mitochondrial respiration to produce ATP. Thus, it appears that aerobic organisms may have adaptive mechanisms to modulate lipid metabolism in response to changes in oxygen availability. In this study, we have demonstrated that hypoxic condition suppresses fasting‐induced lipolysis in the intestinal cells of C. elegans . Similarly, hypoxia also suppressed PKA‐mediated lipolysis of mammalian adipocytes, indicating that there might be evolutionarily conserved regulatory pathways for metabolic regulation upon oxygen. In fasted worms, we have identified hypoxia inducible factor‐1(HIF‐1) as one of key factors in the suppression of PKA‐mediated lipolysis. HIF‐1 induction by inhibition of von Hippel‐Lindau tumor suppressor‐1(VHL‐1), and egg laying defective‐9(EGL‐9) prevented decreased neutral lipid contents upon fasting. Additionally, we observed that suppression of stimulated lipolysis is also mediated by HIF‐1 independent pathway including mitochondrial dysfunction. Together, our data have suggested that the decrease of lipolysis under hypoxic condition is an adaptive response to prevent accumulation of futile free fatty acids which may preserve stored lipid metabolites for energy homeostasis. Support or Funding Information This work was supported by National Creative Research Initiative Program (2011‐0018312) funded by the ministry of Education, Science, and Technology (MEST). Ji Seul Han, Jinuk Kong, and Yul Ji were supported by the BK21 program, Korea.