PMID- 33926085
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20210823
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 12
IP  - 5
DP  - 2021 Apr 26
TI  - The Role of Lipid Sensing Nuclear Receptors (PPARs and LXR) and Metabolic Lipases 
      in Obesity, Diabetes and NAFLD.
LID - 10.3390/genes12050645 [doi]
LID - 645
AB  - Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders characterized 
      by metabolic inflexibility with multiple pathological organ manifestations, 
      including non-alcoholic fatty liver disease (NAFLD). Nuclear receptors are 
      ligand-dependent transcription factors with a multifaceted role in controlling 
      many metabolic activities, such as regulation of genes involved in lipid and 
      glucose metabolism and modulation of inflammatory genes. The activity of nuclear 
      receptors is key in maintaining metabolic flexibility. Their activity depends on 
      the availability of endogenous ligands, like fatty acids or oxysterols, and their 
      derivatives produced by the catabolic action of metabolic lipases, most of which 
      are under the control of nuclear receptors. For example, adipose triglyceride 
      lipase (ATGL) is activated by peroxisome proliferator-activated receptor gamma 
      (PPARgamma) and conversely releases fatty acids as ligands for PPARalpha, therefore, 
      demonstrating the interdependency of nuclear receptors and lipases. The diverse 
      biological functions and importance of nuclear receptors in metabolic syndrome 
      and NAFLD has led to substantial effort to target them therapeutically. This 
      review summarizes recent findings on the roles of lipases and selected nuclear 
      receptors, PPARs, and liver X receptor (LXR) in obesity, diabetes, and NAFLD.
FAU - Dixon, Emmanuel D
AU  - Dixon ED
AD  - Hans Popper Laboratory of Molecular Hepatology, Department of Internal Medicine 
      III, Division of Gastroenterology and Hepatology, Medical University of Vienna, 
      1090 Wien, Austria.
FAU - Nardo, Alexander D
AU  - Nardo AD
AD  - Hans Popper Laboratory of Molecular Hepatology, Department of Internal Medicine 
      III, Division of Gastroenterology and Hepatology, Medical University of Vienna, 
      1090 Wien, Austria.
FAU - Claudel, Thierry
AU  - Claudel T
AUID- ORCID: 0000-0002-5601-9830
AD  - Hans Popper Laboratory of Molecular Hepatology, Department of Internal Medicine 
      III, Division of Gastroenterology and Hepatology, Medical University of Vienna, 
      1090 Wien, Austria.
FAU - Trauner, Michael
AU  - Trauner M
AUID- ORCID: 0000-0002-1275-6425
AD  - Hans Popper Laboratory of Molecular Hepatology, Department of Internal Medicine 
      III, Division of Gastroenterology and Hepatology, Medical University of Vienna, 
      1090 Wien, Austria.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210426
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (Liver X Receptors)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - EC 3.1.1.3 (Lipase)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus/*metabolism
MH  - Humans
MH  - Lipase/genetics/*metabolism
MH  - Liver X Receptors/genetics/*metabolism
MH  - Non-alcoholic Fatty Liver Disease/*metabolism
MH  - Obesity/*metabolism
MH  - Peroxisome Proliferator-Activated Receptors/genetics/*metabolism
PMC - PMC8145571
OTO - NOTNLM
OT  - NAFLD
OT  - diabetes
OT  - metabolic lipase
OT  - nuclear receptor
OT  - obesity
COIS- M.T. has received research grants from Albireo, Cymabay, Falk, Gilead, Intercept, 
      Merck Sharp & Dohme (MSD) and Takeda and travel grants from Abbvie, Falk, Gilead 
      and Intercept. He further has advised for Albireo, BiomX, Boehringer Ingelheim, 
      Falk Pharma GmbH, Genfit, Gilead, Intercept, Jannsen, MSD, Novartis, Phenex, 
      Regulus and Shire and has served as speaker for Falk, Gilead, Intercept and MSD. 
      He is a co-inventor of patents for the medical use of norUDCA 
      (nor-ursodeoxycholic acid) filed by the Medical Universities of Graz and Vienna. 
      All other authors have no conflicts of interest to declare.
EDAT- 2021/05/01 06:00
MHDA- 2021/08/24 06:00
PMCR- 2021/04/26
CRDT- 2021/04/30 01:34
PHST- 2021/03/16 00:00 [received]
PHST- 2021/04/23 00:00 [revised]
PHST- 2021/04/23 00:00 [accepted]
PHST- 2021/04/30 01:34 [entrez]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PHST- 2021/04/26 00:00 [pmc-release]
AID - genes12050645 [pii]
AID - genes-12-00645 [pii]
AID - 10.3390/genes12050645 [doi]
PST - epublish
SO  - Genes (Basel). 2021 Apr 26;12(5):645. doi: 10.3390/genes12050645.