Caffeine enhances lipolysis in primary rat adipocytes via adenosine A1 receptor pathway.

Caffeine is a well-known compound broadly consumed by humans as an ingredient in beverages. Its ingestion is associated with numerous beneficial effects on the organism. Caffeine may, among others, reduce adipose tissue accumulation. However, the mechanism underlying this action is poorly elucidated. Lipolysis is a relevant process directly related to adipocyte metabolism. The present study explored the short-term (2-h) effects of 1 mM caffeine on the lipolytic activity of isolated adipocytes. Lipolysis was measured as the quantity of glycerol released from cells. The expression of lipolysis-related genes was also determined at the mRNA level. It was shown that caffeine significantly increased lipolysis induced by epinephrine (an adrenergic receptor agonist), forskolin (a direct activator of adenylate cyclase (AC)), and dibutyryl-cAMP (a direct stimulator of protein kinase A (PKA)). However, the lipolytic response of fat cells to DPCPX (an adenosine A1 receptor antagonist) was unchanged by caffeine. Moreover, caffeine failed to affect lipolysis stimulated by the combination of DPCPX with epinephrine, DPCPX with DB-cAMP and DPCPX with forskolin. Additionally, the stimulatory effect of caffeine on epinephrine-induced glycerol release was suppressed by H-89 (a direct inhibitor of PKA). Caffeine slightly increased the cAMP content (a signaling molecule increasing the lipolytic process) in adipocytes. However, the expression of analyzed genes was not significantly affected in the presence of the tested compound. The results show that caffeine promotes lipolysis in primary rat adipocytes by inhibiting the adenosine A1 receptor signaling pathway. The pharmacological suppression of PKA abolishes the stimulatory effect. Increased lipolysis in the presence of caffeine contributes to reduced lipid accumulation in adipocytes.