Lithospermum erythrorhizon Root and its Naphthoquinones Repress SREBP1c and Activate PGC1α Through AMPKα
| Autor: | John F. Rebhun, Rodney A. Velliquette, Kelly M. Glynn, Arun Rajgopal |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Nutrition and Dietetics biology Chemistry Endocrinology Diabetes and Metabolism Response element Medicine (miscellaneous) AMPK Lithospermum erythrorhizon biology.organism_classification Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology Mitochondrial biogenesis 030220 oncology & carcinogenesis Gene expression Lipogenesis Coactivator Protein kinase A |
| Zdroj: | Obesity. 26:126-134 |
| ISSN: | 1930-7381 |
| Popis: | Objective To examine specific molecular mechanisms involved in modulating hepatic lipogenesis and mitochondria biogenesis signals by Lithospermum erythrorhizon (gromwell) root extract. Methods Stable cell lines with luciferase reporter constructs were generated to examine sterol regulatory element binding protein 1c (SREBP1c) and peroxisome proliferator-activated receptor gamma, coactivator 1 (PGC1) α promoter activity and estrogen-related receptor (ERR) α response element activity. Gene expression of SREBP1c, stearoyl coenzyme A desaturase 1, and PGC1α was measured by using reverse transcription polymerase chain reaction. Lipogenesis was measured in human hepatoma cells with Nile red staining and flow cytometry. Phosphorylation of AMP-activated protein kinase (AMPK) α was determined by using ELISA and Western blot. Results Gromwell root extract and its naphthoquinones dose-dependently repressed high glucose and liver X receptor α induction of SREBP1c promoter activity and gene expression. Hepatic lipogenesis was repressed, and PGC1α promoter and gene expression and ERRα response element activity were increased by gromwell root extract. Gromwell root extract, shikonin, and α-methyl-n-butyrylshikonin increased AMPKα phosphorylation, and inhibition of AMPK blunted the repression in SREBP1c promoter activity by gromwell root extract and its naphthoquinones. Conclusions Data suggest that gromwell root extract and its naphthoquinones repress lipogenesis by increasing the phosphorylated state of AMPKα and stimulating mitochondrial biogenesis signals. |
| Databáze: | OpenAIRE |
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