Background and Purpose: The anti-obesity effects of vitalmelon extracts have been well verified in only adipogenesis and lipogenesis of adipocytes and high-fat diet-induced obesity mice except lipolysis. Therefore, we were investigated the novel function of edible vitalmelon fruit water extract (VW) on lipolysis. Methods: The changes in the free glycerol release, cyclic adenosine monophosphate (cAMP)-dependent signaling pathway, and expression of β-oxidation-related regulators were analyzed in 3‐isobutyl‐1‐methylxanthine, dexamethasone, and insulin (MDI)-stimulated 3T3‐L1 adipocytes (MiSt-3T3 adipocytes) after a VW treatment. Results: The successful differentiation of pre-adipocytes was confirmed with increased oil-red O (ORO)-stained lipid accumulation and PPARγ gene transcription. After maturation of adipocytes, the levels of free glycerol, intracellular cAMP, and hormone-sensitive lipase phosphorylation increased in a dose-dependent manner in the MDI+VW-treated group. In addition, the protein and mRNA levels of three β-oxidation-related genes (ACADs, ACO1, and CTP) were remarkably increased in the MiSt-3T3 adipocytes after VW treatment, while ATPCL phosphorylation was decreased. The changes in the expression levels of these proteins were accompanied by alteration on the expression levels of the PPARα transcription factors. The levels of PPARα protein phosphorylation and mRNA transcription in MiSt-3T3 adipocytes increased dose-dependently after the VW treatment. Conclusion: These results show that VW can promote lipolysis by controlling the cAMP-mediated glycerol release pathway and β-oxidation in MiSt-3T3 adipocytes.
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