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Retinoic acid modulates lipid accumulation glucose concentration dependently through inverse regulation of SREBP ‐1 expression in 3T3L1 adipocytes
Author(s) -
Abd Eldaim Mabrouk Attia,
Matsuoka Shinya,
OkamatsuOgura Yuko,
Kamikawa Akihiro,
Ahmed Mohamed Mohamed,
Terao Akira,
Nakajima Keiichi,
Kimura Kazuhiro
Publication year - 2017
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12498
Subject(s) - biology , retinoic acid , sterol regulatory element binding protein , adipogenesis , retinoid x receptor , fatty acid synthase , transfection , peroxisome proliferator activated receptor , extracellular , downregulation and upregulation , nuclear receptor , retinoid , endocrinology , gene expression , lipid metabolism , medicine , cell culture , receptor , microbiology and biotechnology , biochemistry , transcription factor , adipose tissue , gene , genetics
It is well known that retinoic acid ( RA ) suppresses adipogenesis, although there are some contradicting reports. In this study, we examined the effect of extracellular glucose on RA ‐induced suppression of adipogenesis in 3T3L1 cell culture. When the cells were cultured in normal glucose medium ( NG ), the addition of RA suppressed lipid accumulation. However, when cultured in high glucose medium ( HG ), addition of RA to the cells enhanced lipid accumulation. These changes were accompanied by parallel alterations in fatty acid synthase ( FAS ) and sterol regulatory element‐binding protein ( SREBP )‐1 gene expression. Transfection of SREBP ‐1 si RNA suppressed RA ‐induced enhancement of lipid accumulation and FAS expression in the cells cultured with HG . Transfection of the nuclear form of SREBP ‐1a cDNA into the cells cultured with NG inhibited RA ‐induced suppression of lipid accumulation and FAS expression. Moreover, RA ‐ and HG ‐induced SREBP ‐1a expression occurred at the early phase of adipogenesis and was dependent on glucocorticoid to induce liver X receptor ( LXR ) β, peroxisomal proliferator‐activated receptor ( PPAR ) γ and retinoid X receptor ( RXR ), the key nuclear factors influencing the SREBP ‐1a gene expression. These results suggest that RA suppresses and enhances lipid accumulation through extracellular glucose concentration‐dependent modulation of SREBP ‐1 expression.