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Kiros HADDISH,Sulagna MUKHERJEE,MinJi CHOI,Jong Won YUN 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
In the present study, we explored that 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. 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, while decreasing FAS, ACC, C/EBPα, and PPARγ, suggesting enhanced lipolysis and fatty acid oxidation as well as reduced lipogenesis and adipogenesis, respectively. Molecular docking studies elucidated that L-Dopa binds to DRD1 and β3-AR, thereby predicting the potential receptor candidates that activate PKA. Mechanistic studies indicate that the browning potential of L-Dopa in 3T3-L1 white adipocytes is mediated by DRD1 and β3-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. 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.
Kiros Haddish,윤종원 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.5
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 PPARα while decreasing FAS, ACC, C/EBPα, and PPARγ, 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 β3-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 β3-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.
Haddish Kiros,Yun Jong Won 한국미생물·생명공학회 2023 Journal of microbiology and biotechnology Vol.33 No.10
Echinacoside (ECH) is a naturally occurring phenylethanoid glycoside, isolated from Echinacea angustifolia, and this study aimed to analyze its effect on thermogenesis and its interaction with dopaminergic receptors 1 and 5 (DRD1 and DRD5) in 3T3-L1 white adipocytes and mice models. We employed RT-PCR, immunoblot, immunofluorescence, a staining method, and an assay kit to determine its impact. ECH showed a substantial increase in browning signals in vitro and a decrease in adipogenic signals in vivo. Additionally, analysis of the iWAT showed that the key genes involved in beiging, mitochondrial biogenesis, and ATP-dependent thermogenesis were upregulated while adipogenesis and lipogenesis genes were downregulated. OXPHOS complexes, Ca2+ signaling proteins as well as intracellular Ca2+ levelswere also upregulated in 3T3-L1 adipocytes following ECH treatment. This was collectively explained by mechanistic studies which showed that ECH mediated the beiging process via the DRD1/5-cAMP-PKA and subsequent downstream molecules, whereas it co-mediated the α1-AR-signaling thermogenesis via the DRD1/5/SERCA2b/RyR2/CKmt pathway in 3T3-L1 adipocytes. Animal experiments revealed that there was a 12.28% reduction in body weight gain after the ECH treatment for six weeks. The effects of ECH treatment on adipose tissue can offer more insights into the treatment of obesity and metabolic syndrome.