Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients

Abstract

Background A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene ( OB ) expression in adipocytes from obese and hypertensive patients. Methods Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 μmol/L), NE (1.0 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L), and from five nonobese and normotensive controls treated with DA (1 μmol/L), NE (1 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L). Results A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients. Conclusion These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients.

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).…”

Novel Trajectories of Bromocriptine Antidiabetic Action: Leptin-IL-6/ JAK2/p-STAT3/SOCS3, p-IR/p-AKT/GLUT4, PPAR-γ/Adiponectin, Nrf2/PARP-1, and GLP-1

“…Skeletal muscles, per se , have a critical role in the production and secretion of several cytokines or myokines that exert autocrine, paracrine, or endocrine effects ( Pedersen et al, 2007 ; Lightfoot and Cooper, 2016 ). On the molecular level, BC opposed the diabetic effect and turned off the JAK2/ p -STAT3/SOCS3 axis by abating its two triggers; viz., IL-6 and leptin ( Alvarez-Aguilar et al, 2013 ). These cytokines stimulate this cascade upon binding to their muscular cytokine receptors ( Lubis et al, 2008 ; Sarvas et al, 2013 ; Wunderlich et al, 2013 ), to phosphorylate JAK2 and STAT3.…”

Effects of postnatal bromocriptine injection on thyroid function and prolactinemia of rats at adulthood

“…Besides, thyroid hormones exert important role in thermogenesis (Pétervári et al, 2005;Silva, 2011). All these hormones are influenced by dopamine (Kaptein et al, 1980;Gonzalez-Iglesias et al, 2008;Ustione and Piston, 2012;Alvarez-Aguilar et al, 2013), so it is plausible that improper neonatal dopaminergic stimulation may permanently alter some of these hormones parameters, explaining the observed changes in food consumption and metabolism.…”