Access Type
Open Access Dissertation
Date of Award
January 2015
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Molecular Biology and Genetics
First Advisor
Kezhong Zhang
Abstract
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.
Recommended Citation
Zheng, Ze, "Crebh, A Novel Liver Clock Keeper For Energy Metabolism" (2015). Wayne State University Dissertations. 1180.
https://digitalcommons.wayne.edu/oa_dissertations/1180
Included in
Endocrinology Commons, Genetics Commons, Molecular Biology Commons