PMID- 31024446
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200225
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 10
DP  - 2019
TI  - ERRalpha as a Bridge Between Transcription and Function: Role in Liver Metabolism and 
      Disease.
PG  - 206
LID - 10.3389/fendo.2019.00206 [doi]
LID - 206
AB  - As transcriptional factors, nuclear receptors (NRs) function as major regulators 
      of gene expression. In particular, dysregulation of NR activity has been shown to 
      significantly alter metabolic homeostasis in various contexts leading to 
      metabolic disorders and cancers. The orphan estrogen-related receptor (ERR) 
      subfamily of NRs, comprised of ERRalpha, ERRbeta, and ERRgamma, for which a natural ligand 
      has yet to be identified, are known as central regulators of energy metabolism. 
      If AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) 
      can be viewed as sensors of the metabolic needs of a cell and responding acutely 
      via post-translational control of proteins, then the ERRs can be regarded as 
      downstream effectors of metabolism via transcriptional regulation of genes for a 
      long-term and sustained adaptive response. In this review, we will focus on 
      recent findings centered on the transcriptional roles played by ERRalpha in 
      hepatocytes. Modulation of ERRalpha activity in both in vitro and in vivo models via 
      genetic or pharmacological manipulation coupled with 
      chromatin-immunoprecipitation (ChIP)-on-chip and ChIP-sequencing (ChIP-seq) 
      studies have been fundamental in delineating the direct roles of ERRalpha in the 
      control of hepatic gene expression. These studies have identified crucial roles 
      for ERRalpha in lipid and carbohydrate metabolism as well as in mitochondrial 
      function under both physiological and pathological conditions. The regulation of 
      ERRalpha expression and activity via ligand-independent modes of action including 
      coregulator binding, post-translational modifications (PTMs) and control of 
      protein stability will be discussed in the context that may serve as valuable 
      tools to modulate ERRalpha function as new therapeutic avenues for the treatment of 
      hepatic metabolic dysfunction and related diseases.
FAU - Xia, Hui
AU  - Xia H
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
AD  - Department of Biochemistry, McGill University, Montreal, QC, Canada.
FAU - Dufour, Catherine R
AU  - Dufour CR
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
FAU - Giguere, Vincent
AU  - Giguere V
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
AD  - Department of Biochemistry, McGill University, Montreal, QC, Canada.
AD  - Medicine and Oncology, McGill University, Montreal, QC, Canada.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190405
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
PMC - PMC6459935
OTO - NOTNLM
OT  - diabetes
OT  - high-fat diet
OT  - inflammation
OT  - liver cancer
OT  - metabolism
OT  - non-alcoholic fatty liver disease
OT  - nuclear receptor
EDAT- 2019/04/27 06:00
MHDA- 2019/04/27 06:01
PMCR- 2019/01/01
CRDT- 2019/04/27 06:00
PHST- 2018/12/18 00:00 [received]
PHST- 2019/03/13 00:00 [accepted]
PHST- 2019/04/27 06:00 [entrez]
PHST- 2019/04/27 06:00 [pubmed]
PHST- 2019/04/27 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2019.00206 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2019 Apr 5;10:206. doi: 10.3389/fendo.2019.00206. 
      eCollection 2019.