Crebh, A Novel Liver Clock Keeper For Energy Metabolism

<p>Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and disease. Cyclic AMP responsive element binding protein 3-like 3 (CREB3L3, also known as CREBH) is a liver-enriched, endoplasmic reticulum (ER)-tethered transcription factor known to regulate hepatic acute-phase response and energy homeostasis under stress conditions. Here, we demonstrate that CREBH is regulated by the circadian clock and functions as a diurnal regulator of hepatic lipid and glucose metabolism. CREBH is required to maintain circadian profiles of blood triglycerides, fatty acids, and glucose as well as hepatic glycogen storage. CREBH rhythmically regulates expression levels and amplitudes of the key genes involved in bi-directional metabolic pathways of both energy utilization and storage. CREBH regulates, and interacts with, the circadian transcriptional activators PPARα and C/EBPβ or the repressor E4BP4 to modulate CREBH transcriptional activities. CREBH deficiency leads to hyper-locomotion, increased metabolic rates, and phase-shifted feeding behavior in mice. In summary, our studies reveal that CREBH functions as a liver metabolic regulator that integrates energy metabolism with circadian rhythm.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Molecular Biology and Genetics

Year dc:date.available

2015

Author dc:creator

• Zheng, Ze

Contributors dc:contributor

• Kezhong Zhang

• circadian rhythm
• CREB3L3
• CREBH
• energy homeostasis
• feeding behavior
• liver metabolism
• Endocrinology
• Genetics
• Molecular Biology

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/1180

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-2179