| First Author | Zhang M | Year | 2018 |
| Journal | Redox Biol | Volume | 16 |
| Pages | 87-96 | PubMed ID | 29482168 |
| Mgi Jnum | J:273678 | Mgi Id | MGI:6282354 |
| Doi | 10.1016/j.redox.2018.01.013 | Citation | Zhang M, et al. (2018) Fasting exacerbates hepatic growth differentiation factor 15 to promote fatty acid beta-oxidation and ketogenesis via activating XBP1 signaling in liver. Redox Biol 16:87-96 |
| abstractText | Liver coordinates a series of metabolic adaptations to maintain systemic energy balance and provide adequate nutrients for critical organs, tissues and cells during starvation. However, the mediator(s) implicated in orchestrating these fasting-induced adaptive responses and the underlying molecular mechanisms are still obscure. Here we show that hepatic growth differentiation factor 15 (GDF15) is regulated by IRE1alpha-XBP1s branch and promotes hepatic fatty acids beta-oxidation and ketogenesis upon fasting. GDF15 expression was exacerbated in liver of mice subjected to long-term fasted or ketogenic diet feeding. Abrogation of hepatic Gdf15 dramatically attenuated hepatic beta-oxidation and ketogenesis in fasted mice or mice with STZ-initiated type I diabetes. Further study revealed that XBP1s activated Gdf15 transcription via binding to its promoter. Elevated GDF15 in liver reduced lipid accumulation and impaired NALFD development in obese mice through enhancing fatty acids oxidation in liver. Therefore, our results demonstrate a novel and critical role of hepatic GDF15 activated by IRE1alpha-XBP1s branch in regulating adaptive responses of liver upon starvation stress. |
