Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1866, Issue 1, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbalip.2020.158812
Keywords
Lutein; 3T3-L1 cells; Adipocyte differentiation; PPAR-gamma; CEBP-alpha; Early phase regulators
Funding
- University Grants Commission (UGC), New Delhi, India
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The study found that lutein significantly reduces the accumulation of lipid droplets, inhibits the expression of CEBP-alpha and PPAR-gamma, and further blocks the gene expression of FAS, FABP4, and SCD1 in mature adipocytes. In the early stages, lutein prevents adipocyte differentiation by blocking the protein expression of CEBP-alpha and PPAR-gamma.
A comprehensive molecular mechanistic role of lutein on adipogenesis is not well understood. The present study focused to evaluate the effect of lutein at the early and late phase of adipocyte differentiation in vitro using a 3T3-L1 cell model. The effect of purified carotenoid on the viability of normal and differentiated 3T3-L1 cells was analyzed by WST-1 assay. Oil Red O and Nile red staining were employed to observe lipid droplets in mature adipocytes. The effect of lutein on gene and protein expression of major transcription factors and adipogenic markers was analyzed by RT-PCR and western blotting, respectively. The role of lutein on mitotic clonal expansion was analyzed by flow cytometry. The results showed a significant reduction (p < 0.05) in the accumulation of lipid droplets in lutein-treated (5 mu M) cells. Inhibition in lipid accumulation was associated with down-regulated expression of CEBP-alpha and PPAR-gamma at gene and protein levels. Subsequently, lutein repressed gene expression of FAS, FABP4, and SCD1 in mature adipocytes. Interestingly, it blocks the protein expression of CEBP-alpha and PPAR-gamma in the initial stages of adipocyte differentiation. This early-stage inhibition of adipocyte differentiation is linked with repressed phosphorylation AKT and ERK. Further, upregulated cyclin D and down-regulated CDK4 and CDK2 in lutein treated adipocytes enumerate its role in delaying the cell cycle progression at the G0/G1 phase. Our results emphasize that adipogenesis inhibitory efficacy of lutein is potentiated by halting early phase regulators of adipocyte differentiation, which strengthens the competency of lutein besides its inevitable presence in the human body.
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