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Circulating Dopamine Is Regulated by Dietary Glucose and Controls Glucagon-like 1 Peptide Action in White Adipose Tissue

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Resumo:Dopamine directly acts in the liver and white adipose tissue (WAT) to regulate insulin signaling, glucose uptake, and catabolic activity. Given that dopamine is secreted by the gut and regulates insulin secretion in the pancreas, we aimed to determine its regulation by nutritional cues and its role in regulating glucagon-like peptide 1 (GLP-1) action in WAT. Solutions with different nutrients were administered to Wistar rats and postprandial dopamine levels showed elevations following a mixed meal and glucose intake. In high-fat diet-fed diabetic Goto-Kakizaki rats, sleeve gastrectomy upregulated dopaminergic machinery, showing the role of the gut in dopamine signaling in WAT. Bromocriptine treatment in the same model increased GLP-1R in WAT, showing the role of dopamine in regulating GLP-1R. By contrast, treatment with the GLP-1 receptor agonist Liraglutide had no impact on dopamine receptors. GLP-1 and dopamine crosstalk was shown in rat WAT explants, since dopamine upregulated GLP-1-induced AMPK activity in mesenteric WAT in the presence of the D2R and D3R inhibitor Domperidone. In human WAT, dopamine receptor 1 (D1DR) and GLP-1R expression were correlated. Our results point out a dietary and gut regulation of plasma dopamine, acting in the WAT to regulate GLP-1 action. Together with the known dopamine action in the pancreas, such results may identify new therapeutic opportunities to improve metabolic control in metabolic disorders.
Autores principais:Tavares, Gabriela
Outros Autores:Rosendo-Silva, Daniela; Simões, Flávia; Eickhoff, Hans; Marques, Daniela; Sacramento, Joana F.; Capucho, Adriana M.; Seiça, Raquel; Conde, Sílvia V.; V Conde, Silvia; Matafome, Paulo
Assunto:dopamine GLP-1 white adipose tissue Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being
Ano:2023
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL

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