PMID- 30912978
OWN - NLM
STAT- MEDLINE
DCOM- 20200526
LR  - 20210109
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 33
IP  - 7
DP  - 2019 Jul
TI  - Regulation of hepatic autophagy by stress-sensing transcription factor CREBH.
PG  - 7896-7914
LID - 10.1096/fj.201802528R [doi]
AB  - Autophagy, a lysosomal degradative pathway in response to nutrient limitation, 
      plays an important regulatory role in lipid homeostasis upon energy demands. 
      Here, we demonstrated that the endoplasmic reticulum-tethered, stress-sensing 
      transcription factor cAMP-responsive element-binding protein, hepatic-specific 
      (CREBH) functions as a major transcriptional regulator of hepatic autophagy and 
      lysosomal biogenesis in response to nutritional or circadian signals. CREBH 
      deficiency led to decreased hepatic autophagic activities and increased hepatic 
      lipid accumulation upon starvation. Under unfed or during energy-demanding phases 
      of the circadian cycle, CREBH is activated to drive expression of the genes 
      encoding the key enzymes or regulators in autophagosome formation or autophagic 
      process, including microtubule-associated protein 1B-light chain 3, 
      autophagy-related protein (ATG)7, ATG2b, and autophagosome formation Unc-51 like 
      kinase 1, and the genes encoding functions in lysosomal biogenesis and 
      homeostasis. Upon nutrient starvation, CREBH regulates and interacts with 
      peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma coactivator 1alpha to 
      synergistically drive expression of the key autophagy genes and transcription 
      factor EB, a master regulator of lysosomal biogenesis. Furthermore, CREBH 
      regulates rhythmic expression of the key autophagy genes in the liver in a 
      circadian-dependent manner. In summary, we identified CREBH as a key 
      transcriptional regulator of hepatic autophagy and lysosomal biogenesis for the 
      purpose of maintaining hepatic lipid homeostasis under nutritional stress or 
      circadian oscillation.-Kim, H., Williams, D., Qiu, Y., Song, Z., Yang, Z., 
      Kimler, V., Goldberg, A., Zhang, R., Yang, Z., Chen, X., Wang, L., Fang, D., Lin, 
      J. D., Zhang, K. Regulation of hepatic autophagy by stress-sensing transcription 
      factor CREBH.
FAU - Kim, Hyunbae
AU  - Kim H
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, Michigan‎, USA.
FAU - Williams, Dreana
AU  - Williams D
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, Michigan‎, USA.
FAU - Qiu, Yining
AU  - Qiu Y
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Song, Zhenfeng
AU  - Song Z
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, Michigan‎, USA.
FAU - Yang, Zhao
AU  - Yang Z
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, Michigan‎, USA.
FAU - Kimler, Victoria
AU  - Kimler V
AD  - Eye Research Institute, Oakland University, Rochester, Michigan‎, USA.
FAU - Goldberg, Andrew
AU  - Goldberg A
AD  - Eye Research Institute, Oakland University, Rochester, Michigan‎, USA.
FAU - Zhang, Ren
AU  - Zhang R
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, Michigan‎, USA.
FAU - Yang, Zengquan
AU  - Yang Z
AD  - Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
FAU - Chen, Xuequn
AU  - Chen X
AD  - Department of Physiology, Wayne State University School of Medicine, Detroit, 
      Michigan‎, USA.
FAU - Wang, Li
AU  - Wang L
AD  - Department of Physiology and Neurobiology-Institute for Systems Genomics, 
      University of Connecticut, Storrs, Connecticut, USA.
AD  - Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA.
AD  - Department of Internal Medicine, Liver Center, Yale University, New Haven, 
      Connecticut, USA.
FAU - Fang, Deyu
AU  - Fang D
AD  - Department of Pathology, Northwestern University Feinberg School of Medicine, 
      Chicago, Illinois, USA.
FAU - Lin, Jiandie D
AU  - Lin JD
AD  - Life Sciences Institute, University of Michigan Medical School, Ann Arbor, 
      Michigan, USA.
FAU - Zhang, Kezhong
AU  - Zhang K
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, Michigan‎, USA.
AD  - Department of Biochemistry, Microbiology, and Immunology, Wayne State University 
      School of Medicine, Wayne State University, Detroit, Michigan, USA.
AD  - Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
LA  - eng
GR  - R01 EY025291/EY/NEI NIH HHS/United States
GR  - R01 DK090313/DK/NIDDK NIH HHS/United States
GR  - R21 ES017829/ES/NIEHS NIH HHS/United States
GR  - R01 DK102456/DK/NIDDK NIH HHS/United States
GR  - P30 DK020572/DK/NIDDK NIH HHS/United States
GR  - R01 DK120330/DK/NIDDK NIH HHS/United States
GR  - R01 DK110314/DK/NIDDK NIH HHS/United States
GR  - R01 AR066634/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190326
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (Creb3l3 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (PPAR alpha)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Tcfeb protein, mouse)
SB  - IM
EIN - FASEB J. 2020 Aug;34(8):11311. PMID: 33405285
MH  - Animals
MH  - Autophagosomes/metabolism
MH  - Autophagy/genetics/*physiology
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Circadian Rhythm
MH  - Cyclic AMP Response Element-Binding Protein/deficiency/*physiology
MH  - Fatty Liver/etiology/genetics/metabolism
MH  - Food Deprivation/*physiology
MH  - Gene Expression Regulation/*physiology
MH  - Hepatocytes/metabolism
MH  - Lipid Metabolism
MH  - Liver/cytology/*metabolism
MH  - Lysosomes/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - PPAR alpha/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
MH  - Stress, Physiological/genetics/physiology
MH  - Transcription, Genetic
PMC - PMC6593881
OTO - NOTNLM
OT  - hepatic lipid homeostasis
OT  - stress response
OT  - transcriptional regulation
COIS- Portions of this work were supported by U.S. National Institutes of Health (NIH), 
      National Institute of Diabetes and Digestive and Kidney Diseases Grants DK090313 
      (to K.Z), DK110314 (to X.C.), and DK102456 (to J.D.L.); NIH National Institute of 
      Environmental Health Sciences Grant ES017829 (to K.Z.); NIH National Institute of 
      Arthritis and Musculoskeletal and Skin Diseases Grant AR066634 (to D.F. and 
      K.Z.); NIH National Eye Institute Grant EY025291 (to A.G.); and American Heart 
      Association Grants 0635423Z and 09GRNT2280479 (to K.Z.). The authors declare no 
      conflicts of interest.
EDAT- 2019/03/27 06:00
MHDA- 2020/05/27 06:00
PMCR- 2020/03/26
CRDT- 2019/03/27 06:00
PHST- 2019/03/27 06:00 [pubmed]
PHST- 2020/05/27 06:00 [medline]
PHST- 2019/03/27 06:00 [entrez]
PHST- 2020/03/26 00:00 [pmc-release]
AID - FJ_201802528R [pii]
AID - 10.1096/fj.201802528R [doi]
PST - ppublish
SO  - FASEB J. 2019 Jul;33(7):7896-7914. doi: 10.1096/fj.201802528R. Epub 2019 Mar 26.