Ghrelin and Des-Acyl Ghrelin Block Fat Breakdown in Rat Adipocytes

While ghrelin is widely recognized for its roles in appetite stimulation and growth hormone release, its direct influence on adipocyte (fat cell) metabolism, particularly the specific receptor mechanisms involved in lipolysis (fat breakdown), remains an area of active research. Isoproterenol is a common pharmacological agent used to induce lipolysis in experimental settings. This study aimed to investigate how both ghrelin and its unacylated form, des-acyl ghrelin, affect isoproterenol-induced lipolysis and to identify the receptor type mediating these effects, specifically addressing the knowledge gap regarding non-GHS-R1a receptor involvement.

Both ghrelin and des-acyl ghrelin significantly inhibited isoproterenol-induced lipolysis in a dose-dependent manner. Ghrelin demonstrated a potent effect, reducing glycerol release by up to 45% at its highest concentration (1 µM) compared to isoproterenol alone. Des-acyl ghrelin also showed a robust inhibitory effect, leading to a 30% reduction in glycerol release at 1 µM. The inhibitory effects were observed across multiple concentrations, with ghrelin consistently showing a slightly stronger effect. The anti-lipolytic actions of both ghrelin and des-acyl ghrelin were completely unaffected by the presence of a specific GHS-R1a antagonist, indicating a novel, non-GHS-R1a mediated mechanism. Furthermore, pre-treatment with pertussis toxin significantly attenuated the inhibitory actions of both peptides, suggesting the involvement of a Gi/o protein-coupled receptor pathway.