PMID- 32916992
OWN - NLM
STAT- MEDLINE
DCOM- 20210406
LR  - 20210503
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 25
IP  - 18
DP  - 2020 Sep 9
TI  - LRRK2 Regulates CPT1A to Promote beta-Oxidation in HepG2 Cells.
LID - 10.3390/molecules25184122 [doi]
LID - 4122
AB  - Leucine-rich repeat kinase 2 (LRRK2) is involved in lipid metabolism; however, 
      the role of LRRK2 in lipid metabolism to affect non-alcoholic fatty liver disease 
      (NAFLD) is still unclear. In the mouse model of NAFLD induced by a high-fat diet, 
      we observed that LRRK2 was decreased in livers. In HepG2 cells, exposure to 
      palmitic acid (PA) down-regulated LRRK2. Overexpression and knockdown of LRRK2 in 
      HepG2 cells were performed to further investigate the roles of LRRK2 in lipid 
      metabolism. Our results showed that beta-oxidation in HepG2 cells was promoted by 
      LRRK2 overexpression, whereas LRRK2 knockdown inhibited beta-oxidation. The critical 
      enzyme of beta-oxidation, carnitine palmitoyltransferase 1A (CPT1A), was positively 
      regulated by LRRK2. Our data suggested that the regulation of CPT1A by LRRK2 may 
      be via the activation of AMP-activated protein kinase (AMPK) and peroxisome 
      proliferator-activated receptor alpha (PPARalpha). The overexpression of LRRK2 reduced 
      the concentration of a pro-inflammatory cytokine, tumor necrosis factor alpha (TNFalpha), 
      induced by PA. The increase in beta-oxidation may promote lipid catabolism to 
      suppress inflammation induced by PA. These results indicated that LRRK2 
      participated in the regulation of beta-oxidation and suggested that the decreased 
      LRRK2 may promote inflammation by suppressing beta-oxidation in the liver.
FAU - Lin, Chiao-Wei
AU  - Lin CW
AD  - Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan.
AD  - Department of Animal Science and Technology, National Taiwan University, Taipei 
      106, Taiwan.
FAU - Peng, Yu-Ju
AU  - Peng YJ
AD  - Department of Animal Science and Technology, National Taiwan University, Taipei 
      106, Taiwan.
FAU - Lin, Yuan-Yu
AU  - Lin YY
AUID- ORCID: 0000-0002-3397-3218
AD  - Department of Animal Science and Technology, National Taiwan University, Taipei 
      106, Taiwan.
FAU - Mersmann, Harry John
AU  - Mersmann HJ
AD  - Department of Animal Science and Technology, National Taiwan University, Taipei 
      106, Taiwan.
FAU - Ding, Shih-Torng
AU  - Ding ST
AD  - Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan.
AD  - Department of Animal Science and Technology, National Taiwan University, Taipei 
      106, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20200909
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Cytokines)
RN  - 0 (PPAR alpha)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - EC 2.3.1.21 (CPT1A protein, human)
RN  - EC 2.3.1.21 (CPT1B protein, mouse)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - EC 2.7.11.1 (LRRK2 protein, human)
RN  - EC 2.7.11.1 (Leucine-Rich Repeat Serine-Threonine Protein Kinase-2)
RN  - EC 2.7.11.1 (Lrrk2 protein, mouse)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Carnitine O-Palmitoyltransferase/*physiology
MH  - Cell Nucleus/metabolism
MH  - Cytokines/metabolism
MH  - Diet, High-Fat
MH  - Hep G2 Cells
MH  - Humans
MH  - Inflammation
MH  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/*physiology
MH  - Lipid Metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Non-alcoholic Fatty Liver Disease/metabolism
MH  - Oxidation-Reduction
MH  - Oxygen/*metabolism
MH  - PPAR alpha/metabolism
MH  - Palmitic Acid/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC7570678
OTO - NOTNLM
OT  - CPT1A
OT  - LRRK2
OT  - NAFLD
OT  - beta-oxidation
COIS- The authors declare no conflict of interest.
EDAT- 2020/09/13 06:00
MHDA- 2021/04/07 06:00
PMCR- 2020/09/09
CRDT- 2020/09/12 01:02
PHST- 2020/08/18 00:00 [received]
PHST- 2020/09/08 00:00 [revised]
PHST- 2020/09/09 00:00 [accepted]
PHST- 2020/09/12 01:02 [entrez]
PHST- 2020/09/13 06:00 [pubmed]
PHST- 2021/04/07 06:00 [medline]
PHST- 2020/09/09 00:00 [pmc-release]
AID - molecules25184122 [pii]
AID - molecules-25-04122 [pii]
AID - 10.3390/molecules25184122 [doi]
PST - epublish
SO  - Molecules. 2020 Sep 9;25(18):4122. doi: 10.3390/molecules25184122.