Dopamine receptors in human adipocytes: expression and functions

Area of Science:

• Endocrinology
• Metabolic research
• Adipose tissue biology

Background:

• Dopamine (DA) signals through five dopamine receptors (DAR), categorized as D1R-like (cAMP-increasing) or D2R-like (cAMP-decreasing).
• In humans, dopamine sulfate (DA-S) is the predominant circulating form, convertible to bioactive dopamine by arylsulfatase A (ARSA).

Purpose of the Study:

• To investigate the expression of DAR and ARSA in human adipose tissue.
• To determine the regulation of prolactin (PRL) and adipokine expression and release by dopamine.

Main Methods:

• DAR and ARSA expression analyzed via RT-PCR, qPCR, and Western blotting in human adipocytes and cell lines.
• ARSA activity assessed using enzymatic assays.
• PRL, cAMP, cGMP, leptin, adiponectin, and IL-6 levels measured by ELISA, luciferase reporter assays, and Nb2 bioassays.
• MAPK and PI3 kinase/Akt activation determined by Western blotting.

Main Results:

• Dopamine receptors (DAR) are expressed at mRNA and protein levels in human adipose tissue and adipocytes, with expression varying during adipogenesis.
• Arylsulfatase A (ARSA) activity increases in adipocytes post-differentiation.
• Dopamine (DA) at nanomolar concentrations suppresses cAMP, stimulates cGMP, and activates MAPK pathways in adipocytes.
• DA and DA-S inhibit PRL gene expression and release via D2R-like receptors.
• DA stimulates IL-6 and suppresses leptin release via D1R/D5R receptors, while also stimulating adiponectin release.

Conclusions:

• Human adipocytes express functional dopamine receptors (DAR) and arylsulfatase A (ARSA), indicating a peripheral regulatory role for dopamine in adipose tissue function.
• The observed effects suggest dopamine's involvement in modulating adipokine secretion and potentially influencing metabolic homeostasis.
• Antipsychotic medications that activate DAR may contribute to weight gain and metabolic alterations through direct actions on adipose tissue.