Cabergoline counteracts adipose and skeletal muscle lipid accumulation: A novel therapeutic approach to obesity?

OBJECTIVE

Obesity represents a global health problem with large costs for public health. Cabergoline (CAB), a potent dopamine agonist with a high affinity for type 2 dopamine receptor (D2R), usually used in clinical practice for hyperprolactinemia management, has been reported to significantly decrease metabolic syndrome prevalence and visceral adiposity associated with improved insulin sensitivity in prolactinoma patients. Nevertheless, scant data are reported about CAB effects on obesity condition.

METHODS

The current preclinical study investigated the in vivo chronic effects of CAB on obese rat models by exploring energy homeostasis and tissue molecular modifications. Simultaneously, the current study evaluated the in vitro chronic effects of CAB on adipocyte and myocyte models by investigating cellular lipid accumulation, respiration and glucose internalization.

RESULTS

The in vivo study demonstrated for the first time that CAB, chronically administered to an obese rat model, positively impacts body composition, energy balance, insulin secretion, and sensitivity and lipid profile, while outlining the molecular mechanisms fundamentally based on the reduction of the expression of the main markers of lipid accumulation and on the activation of the proteins classically involved in fat oxidation, PKA-Cα and pAMPKα Thr172. The in vitro study further demonstrated that the treatment with CAB, alone or in combination with insulin, significantly reduces lipid accumulation both in adipocytes and myocytes, confirming the in vivo results, by activating catabolic pathways, enhancing respiration in adipocytes and promoting glucose uptake in myocytes.

CONCLUSIONS

The current preclinical study demonstrated that chronic treatment with CAB improves obesity-associated metabolic disorders such as dyslipidemia and hyperinsulinemia, by regulating the expression of lipid accumulation markers and reducing skeletal muscle ectopic lipid accumulation.