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Lithospermum erythrorhizon Root and its Naphthoquinones Repress SREBP1c and Activate PGC1α Through AMPKα
Author(s) -
Velliquette Rodney A.,
Rajgopal Arun,
Rebhun John,
Glynn Kelly
Publication year - 2018
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.22061
Subject(s) - lipogenesis , ampk , mitochondrial biogenesis , phosphorylation , peroxisome proliferator activated receptor , coactivator , chemistry , microbiology and biotechnology , transcription factor , biology , biochemistry , mitochondrion , protein kinase a , receptor , lipid metabolism , gene
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.