LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells
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...
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MDPI AG
2020-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/18/4122 |
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| author | Chiao-Wei Lin Yu-Ju Peng Yuan-Yu Lin Harry John Mersmann Shih-Torng Ding |
| author_facet | Chiao-Wei Lin Yu-Ju Peng Yuan-Yu Lin Harry John Mersmann Shih-Torng Ding |
| author_sort | Chiao-Wei Lin |
| collection | DOAJ |
| description | 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 β-oxidation in HepG2 cells was promoted by LRRK2 overexpression, whereas LRRK2 knockdown inhibited β-oxidation. The critical enzyme of β-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 α (PPARα). The overexpression of LRRK2 reduced the concentration of a pro-inflammatory cytokine, tumor necrosis factor α (TNFα), induced by PA. The increase in β-oxidation may promote lipid catabolism to suppress inflammation induced by PA. These results indicated that LRRK2 participated in the regulation of β-oxidation and suggested that the decreased LRRK2 may promote inflammation by suppressing β-oxidation in the liver. |
| first_indexed | 2024-03-10T16:27:08Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T16:27:08Z |
| publishDate | 2020-09-01 |
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| series | Molecules |
| spelling | doaj.art-211fcdcc6a09424188ea1fd1fe1e14cf2023-11-20T13:07:28ZengMDPI AGMolecules1420-30492020-09-012518412210.3390/molecules25184122LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 CellsChiao-Wei Lin0Yu-Ju Peng1Yuan-Yu Lin2Harry John Mersmann3Shih-Torng Ding4Institute of Biotechnology, National Taiwan University, Taipei 106, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 106, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 106, TaiwanDepartment of Animal Science and Technology, National Taiwan University, Taipei 106, TaiwanInstitute of Biotechnology, National Taiwan University, Taipei 106, TaiwanLeucine-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 β-oxidation in HepG2 cells was promoted by LRRK2 overexpression, whereas LRRK2 knockdown inhibited β-oxidation. The critical enzyme of β-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 α (PPARα). The overexpression of LRRK2 reduced the concentration of a pro-inflammatory cytokine, tumor necrosis factor α (TNFα), induced by PA. The increase in β-oxidation may promote lipid catabolism to suppress inflammation induced by PA. These results indicated that LRRK2 participated in the regulation of β-oxidation and suggested that the decreased LRRK2 may promote inflammation by suppressing β-oxidation in the liver.https://www.mdpi.com/1420-3049/25/18/4122LRRK2β-oxidationCPT1ANAFLD |
| spellingShingle | Chiao-Wei Lin Yu-Ju Peng Yuan-Yu Lin Harry John Mersmann Shih-Torng Ding LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells Molecules LRRK2 β-oxidation CPT1A NAFLD |
| title | LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells |
| title_full | LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells |
| title_fullStr | LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells |
| title_full_unstemmed | LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells |
| title_short | LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells |
| title_sort | lrrk2 regulates cpt1a to promote β oxidation in hepg2 cells |
| topic | LRRK2 β-oxidation CPT1A NAFLD |
| url | https://www.mdpi.com/1420-3049/25/18/4122 |
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