KMID : 1094720220270050818
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Biotechnology and Bioprocess Engineering 2022 Volume.27 No. 5 p.818 ~ p.832
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L-Dihydroxyphenylalanine (L-Dopa) Induces Brown-like Phenotype in 3T3-L1 White Adipocytes via Activation of Dopaminergic and ¥â3-adrenergic Receptors
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Kiros Haddish
Yun Jong-Won
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Abstract
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Due to its propensity to boost energy expenditure, browning of white fat is emerging as an intriguing and prospective target for therapeutic intervention in obesity. Here, we report that L-dihydroxyphenylalanine (L-Dopa), used as a gold standard therapy in Parkinson¡¯s disease, induces browning in 3T3-L1 adipocytes by increasing the expression levels of beige-specific marker genes such as Cd137, Cited1, Cidea, Tbx1, Prdm16, and Ucp1. In addition, exposure to L-Dopa induces a remarkable increase in the expressions of proteins involved in thermogenesis in white adipocytes. L-Dopa treatment also regulates 3T3-L1 adipocytes by markedly increasing protein expressions of p-AMPK, p-HSL, CPT1, ACOX1, and PPAR¥á while decreasing FAS, ACC, C/EBP¥á, and PPAR¥ã, suggesting enhanced lipolysis and fatty acid oxidation as well as reduced lipogenesis and adipogenesis, respectively. Molecular docking studies elucidated that L-Dopa binds to dopamine receptor D1 (DRD1) and ¥â3-AR, thereby predicting the potential receptor candidates that activate protein kinase A (PKA), the master regulator of lipid metabolism. Mechanistic studies indicate that the browning potential of L-Dopa in 3T3-L1 white adipocytes is mediated by DRD1 and ¥â3-AR activation, which consequently stimulates the PKA/p38 MAPK/ERK signaling pathway. In conclusion, L-Dopa appears to be a promising therapeutic candidate in the fight against obesity due to its inherent role in the browning of 3T3-L1 adipocytes via both the dopaminergic and adrenergic pathways. To our knowledge, this is the first report that demonstrates the browning potential of L-Dopa in white adipocytes. Our results may assist to expand the understanding on the contradictory findings in literature, related to the association between L-Dopa and weight loss observed in Parkinson¡¯s disease patients.
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KEYWORD
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anti-obesity, dopamine, L-Dopa, fat browningl, 3T3-L1 cells
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