title: Dopamine directly increases mitochondrial mass and thermogenesis in brown adipocytes.
abstract: Brown adipose tissue (BAT) is key to energy homeostasis. By virtue of its thermogenic potential, it may dissipate excessive energy, regulate body weight and increase insulin sensitivity. Catecholamines are critically involved in the regulation of BAT thermogenesis, yet research has focussed on the effects of noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT thermogenesis, but the cellular mechanisms involved have not been addressed. We employed our extensively characterised murine brown adipocyte cells. D1-like and D2-like receptors were detectable at the protein level. Stimulation with DA caused an increase in cAMP concentrations. Oxygen consumption rates (OCR), mitochondrial membrane potential (Δψm) and uncoupling protein 1 (UCP1) levels increased after 24 h of treatment with either DA or a D1-like specific receptor agonist. A D1-like receptor antagonist abolished the DA-mediated effect on OCR, Δψmand UCP1. DA induced the release of fatty acids, which did not additionally alter DA-mediated increases of OCR. Mitochondrial mass (as determined by (i) CCCP- and oligomycin-mediated effects on OCR and (ii) immunoblot analysis of mitochondrial proteins) also increased within 24 h. This was accompanied by an increase in peroxisome proliferator-activated receptor gamma co-activator 1 alpha protein levels. Also, DA caused an increase in p38 MAPK phosphorylation and pharmacological inhibition of p38 MAPK abolished the DA-mediated effect on ΔψmIn summary, our study is the first to reveal direct D1-like receptor and p38 MAPK-mediated increases of thermogenesis and mitochondrial mass in brown adipocytes. These results expand our understanding of catecholaminergic effects on BAT thermogenesis.
authors.affiliation: Universität zu LübeckUniversitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I, Lübeck, Germany.
authors.forename: Rose
authors.initials: R
authors.lastname: Kohlie
authors.affiliation: Universität zu LübeckUniversitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I, Lübeck, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Perwitz
authors.affiliation: Universität zu LübeckUniversitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I, Lübeck, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Resch
authors.affiliation: Universität zu LübeckUniversitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I, Lübeck, Germany.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Schmid
authors.affiliation: Universität zu LübeckUniversitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I, Lübeck, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.affiliation: Universität zu LübeckUniversitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I, Lübeck, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Klein
authors.affiliation: Universität zu LübeckUniversitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I, Lübeck, Germany alexander.iwen@uni-luebeck.de.
authors.forename: K Alexander
authors.initials: KA
authors.lastname: Iwen
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D010101:Oxygen Consumption; D011954:Receptors, Dopamine / Q000378:metabolism; D022722:Thermogenesis; D000071256:Uncoupling Protein 1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D011954:Receptors, Dopamine; D000071256:Uncoupling Protein 1; D000242:Cyclic AMP; D048051:p38 Mitogen-Activated Protein Kinases; D004298:Dopamine
keywords: UCP1; brown adipocytes; dopamine; mitochondrial mass; p38 MAPK; thermogenesis