| First Author | Lee JM | Year | 2014 |
| Journal | Nature | Volume | 516 |
| Issue | 7529 | Pages | 112-5 |
| PubMed ID | 25383539 | Mgi Jnum | J:217539 |
| Mgi Id | MGI:5614515 | Doi | 10.1038/nature13961 |
| Citation | Lee JM, et al. (2014) Nutrient-sensing nuclear receptors coordinate autophagy. Nature 516(7529):112-5 |
| abstractText | Autophagy is an evolutionarily conserved catabolic process that recycles nutrients upon starvation and maintains cellular energy homeostasis. Its acute regulation by nutrient-sensing signalling pathways is well described, but its longer-term transcriptional regulation is not. The nuclear receptors peroxisome proliferator-activated receptor-alpha (PPARalpha) and farnesoid X receptor (FXR) are activated in the fasted and fed liver, respectively. Here we show that both PPARalpha and FXR regulate hepatic autophagy in mice. Pharmacological activation of PPARalpha reverses the normal suppression of autophagy in the fed state, inducing autophagic lipid degradation, or lipophagy. This response is lost in PPARalpha knockout (Ppara(-/-), also known as Nr1c1(-/-)) mice, which are partially defective in the induction of autophagy by fasting. Pharmacological activation of the bile acid receptor FXR strongly suppresses the induction of autophagy in the fasting state, and this response is absent in FXR knockout (Fxr(-/-), also known as Nr1h4(-/-)) mice, which show a partial defect in suppression of hepatic autophagy in the fed state. PPARalpha and FXR compete for binding to shared sites in autophagic gene promoters, with opposite transcriptional outputs. These results reveal complementary, interlocking mechanisms for regulation of autophagy by nutrient status. |
