Endocrine Abstracts

Adipose tissue is an endocrine organ releasing adipokines and expressing specific markers and intracellular mediators, which regulate whole-body energy by balancing lipid accumulation and utilization through adipogenesis, the differentiation of preadipocytes into mature adipocytes associated with gradual lipid storage, and lipogenesis, the additional lipid accumulation in mature adipocytes. Adipogenesis and lipogenesis, strongly induced by insulin, occur in white adipocytes, specialized in excess energy storage as fat depots, and in brown and beige adipocytes, specialized in energy storage dissipation. Decreasing white and increasing brown and beige adipogenesis and lipogenesis, may represent therapeutic tools for obesity. This study aims at investigating the effects of the dopamine agonist cabergoline (CAB) on white, brown and beige adipogenesis as well as on basal and insulin-induced lipogenesis. At this purpose, CAB (10^-10 -10^-6 M) was administered in 3T3L1 preadipocytes induced to differentiate, in order to evaluate its effect on white, brown and beige adipogenesis, and in white, brown and beige mature 3T3L1, in order to evaluate its effect on lipogenesis. Adipogenesis and lipogenesis were investigated measuring lipid accumulation using Oil red O staining. Messenger and protein levels of leptin, adiponectin and PPARγ, as white lipogenesis markers and mediators, and of UCP1, PPARγ and PKA, as brown lipogenesis markers and mediators, were analyzed by RT-qPCR and/or WB. During white adipogenesis, CAB10^-8 M and 10^-6 M significantly inhibited lipid accumulation (27-37%; P<0.05) and lipogenesis in absence (63-64%; P<0.001) and presence (85-51%; P<0.0001) of insulin administration, compared to controls, with significant decrease of leptin protein and messenger levels (P<0.01), slight increase of adiponectin protein and slight decrease of PPARγ protein. During brown adipogenesis, CAB10^-10 M-10^-6 M slightly stimulated lipid accumulation (18-24%) and lipogenesis in presence of insulin (15-30%), compared to controls, with slight increase of UCP1 and PPARγ messenger and PPARγ and PKA protein levels. Finally, during beige adipogenesis, CAB10^-10 M-10^-6 M slightly inhibited lipid accumulation (34-38%) and lipogenesis (38-43%), with slight increase of UCP1 and PPARγ messenger levels. In conclusion, the current study demonstrated a novel CAB effect on adipose tissue modulation, defining a pivotal role of dopaminergic system in the obesity pathophysiology.