Dopamine Receptors in Human Adipocytes: Expression and Functions

Abstract

IntroductionDopamine (DA) binds to five receptors (DAR), classified by their ability to increase (D1R-like) or decrease (D2R-like) cAMP. In humans, most DA circulates as dopamine sulfate (DA-S), which can be de-conjugated to bioactive DA by arylsulfatase A (ARSA). The objective was to examine expression of DAR and ARSA in human adipose tissue and determine whether DA regulates prolactin (PRL) and adipokine expression and release.MethodsDAR were analyzed by RT-PCR and Western blotting in explants, primary adipocytes and two human adipocyte cell lines, LS14 and SW872. ARSA expression and activity were determined by qPCR and enzymatic assay. PRL expression and release were determined by luciferase reporter and Nb2 bioassay. Analysis of cAMP, cGMP, leptin, adiponectin and interleukin 6 (IL-6) was done by ELISA. Activation of MAPK and PI3 kinase/Akt was determined by Western blotting.ResultsDAR are variably expressed at the mRNA and protein levels in adipose tissue and adipocytes during adipogenesis. ARSA activity in adipocyte increases after differentiation. DA at nM concentrations suppresses cAMP, stimulates cGMP, and activates MAPK in adipocytes. Acting via D2R-like receptors, DA and DA-S inhibit PRL gene expression and release. Acting via D1R/D5R receptors, DA suppresses leptin and stimulates adiponectin and IL-6 release.ConclusionsThis is the first report that human adipocytes express functional DAR and ARSA, suggesting a regulatory role for peripheral DA in adipose functions. We speculate that the propensity of some DAR-activating antipsychotics to increase weight and alter metabolic homeostasis is due, in part, to their direct action on adipose tissue.

Dopamine D2 receptor upregulates leptin and IL-6 in adipocytes

“…It has been report that dopamine suppresses leptin release in 3T3-L1 cells and in human subcutaneous adipocyte tissue (10,11,12). However, our data show that D 2 R increases leptin expression (Figures 2, 4, and S1).…”

“…Subcutaneous and visceral tissues were collected before and after treatment and no differences were found between groups before treatment on leptin mRNA expression (data not Dopamine has been shown to decrease leptin expression in human subcutaneous adipocyte tissue (10,12). 3T3-L1cells may also express D 2 R (35) ( Figure 1).…”

“…Mouse and human adipocytes express dopamine receptors but their effects on inflammation are controversial. Thus, dopamine has been reported to decrease (10)(11)(12) leptin expression and increase IL-6 expression in adipocytes (10,13). D 1 -like receptor stimulation decreased leptin release but increased IL-6 release in subcutaneous adipocytes from non-obese, non-diabetic humans (10).…”

Dopamine gene methylation patterns are associated with obesity markers and carbohydrate intake

“…The link between body weight regulation and fat storage and dopaminergic signaling may also rely on the endocrine effects of DA in peripheral tissues such as insulin secretion and specific actions on adipocytes (Rubí & Maechler, 2010). Furthermore, human adipose cells express DA receptors during adipogenesis, suggesting a controlling role of DA in adipose tissue processes (Borcherding et al., 2011). …”

Atypical Antipsychotics: Do Their Direct Actions on Adipocytes Contribute to Metabolic Disturbances?

“…Both regulatory and metabolic endpoints such as adipokine secretion, lipolysis, lipogenesis, and glucose uptake can be assessed in these models. For example, using adipocyte cultures, we reported that DA inhibits leptin release, suppresses lipolysis, and stimulates preadipocyte proliferation [14]. We also found that several 5-HTR subtypes are expressed in human adipocytes, and that serotonin inhibits leptin release (unpublished observation).…”