Ethyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes
Xiaoyu Wang,1 Guangbing Li,1,2 Changfa Guo,3 Jiayao Zhang,1 Junjie Kong,1,2 Jingyi He,1,2 Feiyu Li,1 Yong Liu,1 Yang Yang,1 Ziwen Lu,1 Jun Liu1,2 1Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University,...
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2021
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oai:doaj.org-article:13611ef5d5864786961fdd3d49bd4d652021-12-02T18:51:31ZEthyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes1178-7007https://doaj.org/article/13611ef5d5864786961fdd3d49bd4d652021-10-01T00:00:00Zhttps://www.dovepress.com/ethyl-2-234-trimethoxy-6-1-octanoylphenyl-acetate-tmpa-ameliorates-lip-peer-reviewed-fulltext-article-DMSOhttps://doaj.org/toc/1178-7007Xiaoyu Wang,1 Guangbing Li,1,2 Changfa Guo,3 Jiayao Zhang,1 Junjie Kong,1,2 Jingyi He,1,2 Feiyu Li,1 Yong Liu,1 Yang Yang,1 Ziwen Lu,1 Jun Liu1,2 1Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Cheeloo College of Medicine, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Jun LiuDepartment of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of ChinaEmail dr_liujun1967@126.comBackground: The AMP-activated protein kinase alpha (AMPKα) pathway has widely been considered a key factor in energy metabolism. Ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl] acetate (TMPA) is a novel AMPK agonist, which influences the stability of Nuclear Receptor Subfamily 4, Group A, Member 1 (Nur77)-serine-threonine kinase 11 (LKB1) in the nucleus. A recent study has determined that TMPA can ameliorate the reduction of insulin resistance in type II db/db mice. However, the role of TMPA in hepatocyte lipid metabolism has not been elucidated.Objective: To investigate whether TMPA could ameliorate liver lipid accumulation under the stimulation of free fatty acids (FFAs) in vitro.Methods: We evaluated differences of Nur77 and AMPK pathway in mice fed a high-fat diet and those fed a normal diet. In vitro, TMPA was added to HepG2 cells and primary hepatocytes before FFAs stimulation. Oil red O staining, Nile red staining were used to evaluate lipid deposition. Western blot and immunofluorescence were used to quantify related proteins.Results: Nur77, AMPKα, LKB1, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), acetyl-CoA carboxylase phosphorylation (p-ACC), and carnitine palmitoyltransferase 1 (CPT1A) showed significant differences in vivo. Under the intervention of TMPA, HepG2 cells and primary hepatocytes showed considerable amelioration of lipid deposition and improved the expression of phosphorylated (p)-AMPKα (p-AMPKα), p-LKB1, p-ACC, and CPT1A. Furthermore, Western blotting and immunofluorescence studies indicated that LKB1 dramatically increased expression in the cytoplasm but decreased in the nucleus. Further, AMPKα phosphorylation (p-AMPKα) also showed a higher expression in cytoplasm instead of the nucleus.Conclusion: TMPA ameliorated lipid accumulation by influencing the stability of Nur77-LKB1 in vitro.Keywords: ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl] acetate, Nur77, AMPK pathway, HepG2 cells, primary hepatocytesWang XLi GGuo CZhang JKong JHe JLi FLiu YYang YLu ZLiu JDove Medical Pressarticleethyl 2-[234-trimethoxy-6-(1-octanoyl)phenyl] acetatenur77 ;ampk pathwayhepg2 cellsprimary hepatocytesSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 4165-4177 (2021) |
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DOAJ |
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EN |
| topic |
ethyl 2-[2 3 4-trimethoxy-6-(1-octanoyl)phenyl] acetate nur77 ;ampk pathway hepg2 cells primary hepatocytes Specialties of internal medicine RC581-951 |
| spellingShingle |
ethyl 2-[2 3 4-trimethoxy-6-(1-octanoyl)phenyl] acetate nur77 ;ampk pathway hepg2 cells primary hepatocytes Specialties of internal medicine RC581-951 Wang X Li G Guo C Zhang J Kong J He J Li F Liu Y Yang Y Lu Z Liu J Ethyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes |
| description |
Xiaoyu Wang,1 Guangbing Li,1,2 Changfa Guo,3 Jiayao Zhang,1 Junjie Kong,1,2 Jingyi He,1,2 Feiyu Li,1 Yong Liu,1 Yang Yang,1 Ziwen Lu,1 Jun Liu1,2 1Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Cheeloo College of Medicine, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Jun LiuDepartment of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of ChinaEmail dr_liujun1967@126.comBackground: The AMP-activated protein kinase alpha (AMPKα) pathway has widely been considered a key factor in energy metabolism. Ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl] acetate (TMPA) is a novel AMPK agonist, which influences the stability of Nuclear Receptor Subfamily 4, Group A, Member 1 (Nur77)-serine-threonine kinase 11 (LKB1) in the nucleus. A recent study has determined that TMPA can ameliorate the reduction of insulin resistance in type II db/db mice. However, the role of TMPA in hepatocyte lipid metabolism has not been elucidated.Objective: To investigate whether TMPA could ameliorate liver lipid accumulation under the stimulation of free fatty acids (FFAs) in vitro.Methods: We evaluated differences of Nur77 and AMPK pathway in mice fed a high-fat diet and those fed a normal diet. In vitro, TMPA was added to HepG2 cells and primary hepatocytes before FFAs stimulation. Oil red O staining, Nile red staining were used to evaluate lipid deposition. Western blot and immunofluorescence were used to quantify related proteins.Results: Nur77, AMPKα, LKB1, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), acetyl-CoA carboxylase phosphorylation (p-ACC), and carnitine palmitoyltransferase 1 (CPT1A) showed significant differences in vivo. Under the intervention of TMPA, HepG2 cells and primary hepatocytes showed considerable amelioration of lipid deposition and improved the expression of phosphorylated (p)-AMPKα (p-AMPKα), p-LKB1, p-ACC, and CPT1A. Furthermore, Western blotting and immunofluorescence studies indicated that LKB1 dramatically increased expression in the cytoplasm but decreased in the nucleus. Further, AMPKα phosphorylation (p-AMPKα) also showed a higher expression in cytoplasm instead of the nucleus.Conclusion: TMPA ameliorated lipid accumulation by influencing the stability of Nur77-LKB1 in vitro.Keywords: ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl] acetate, Nur77, AMPK pathway, HepG2 cells, primary hepatocytes |
| format |
article |
| author |
Wang X Li G Guo C Zhang J Kong J He J Li F Liu Y Yang Y Lu Z Liu J |
| author_facet |
Wang X Li G Guo C Zhang J Kong J He J Li F Liu Y Yang Y Lu Z Liu J |
| author_sort |
Wang X |
| title |
Ethyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes |
| title_short |
Ethyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes |
| title_full |
Ethyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes |
| title_fullStr |
Ethyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes |
| title_full_unstemmed |
Ethyl 2-[2,3,4-Trimethoxy-6-(1-Octanoyl)Phenyl] Acetate (TMPA) Ameliorates Lipid Accumulation by Disturbing the Combination of LKB1 with Nur77 and Activating the AMPK Pathway in HepG2 Cells and Mice Primary Hepatocytes |
| title_sort |
ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl] acetate (tmpa) ameliorates lipid accumulation by disturbing the combination of lkb1 with nur77 and activating the ampk pathway in hepg2 cells and mice primary hepatocytes |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/13611ef5d5864786961fdd3d49bd4d65 |
| work_keys_str_mv |
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