Endocrine Abstracts

Obesity is caused by an imbalance between dietary energy intake and expenditure. The expression of dopamine receptors (DRs) in human adipocytes has been already demonstrated. Moreover, the effects of cabergoline, a dopamine agonist, on body weight and glucose homeostasis in obese subjects without hyperprolactinemia has already been reported. The current study investigates the effects of cabergoline on lipid accumulation and on adipogenic factors expression to better define the pivotal role of dopaminergic system in obesity etiology. To this purpose, 3T3-L1 cells, the most-well established mouse model for adipogenesis in in vitro studies, were used. Proliferating 3T3L1 cells were suitably differentiated in mature adipocytes and mRNA levels of DRs were monitored during the differentiation process by RT-qPCR. Moreover, effect of escalating doses of cabergoline (10^–8 M and 10^–6 M) alone or combined with 2 × 10^–8 M insulin, on lipid accumulation were investigated through Oil Red O staining after 3 days of treatment. To confirm the anti-lipogenic action of cabergoline, mRNA and protein levels of adipogenic factors were measured by RT-qPCR and WB analysis respectively. Intracellular analysis of pAMPK Thr172 and pAKT Ser473 was performed to confirm anti-lipogenic action of cabergoline by inducing fat β-oxidation process.

3T3-L1 showed increased DRs mRNA levels during differentiation, concomitantly to insulin receptor, with maximum expression levels at day 12 of differentiation. Quantitative measurement of the intracellular oil droplet revealed that after cabergoline 10^–8 M and 10^–6 M, alone and with 2 × 10^–8 M insulin, the lipid content decreases by about 60% compared to control (P < 0.0001). Besides, cabergoline 10^–8 M and 10^–6 M alone and with 2 × 10^–8 M insulin significantly down-regulates leptin gene expression compared to control (P < 0.001). While gene expression of adiponectin and PPARγ remains unchanged after treatment, protein levels of bothare inhibited after 3 days of exposure with cabergoline 10^–6 M alone and with a stronger inhibition when cabergoline was combined with 2 × 10^–8 M insulin. Inhibition of fatty acid synthase and pAKT Ser473 protein expression and activation of pAMPK Thr172 after cabergoline 10^–6 M alone or combined with 2 × 10^–8 M insulin confirm that cabergoline can reduce de novo synthesis and accumulation of lipids by stimulating fat β-oxidation.

In conclusion, these data demonstrated a novel role of cabergoline in the suppression of lipid accumulation by reducing adipogenic- and fatty acid synthesis-related factors expression in mature 3T3-L1 cells. The combination with insulin can increase this effect providing the basis for a novel research addressed to anti-obesity use of cabergoline.