R-Limonene Enhances Differentiation and 2-Deoxy-D-Glucose Uptake in 3T3-L1 Preadipocytes by Activating the Akt Signaling Pathway

Adipocyte is an important place for lipid storage. Defects in lipid storage in adipocytes can lead to lipodystrophy and lipid accumulation in muscle, liver, and other organs. It is the condition of mixed dyslipidemia which may favor the development of insulin resistance via lipotoxic mechanisms. Our objective of the study was to investigate the potential role of R-limonene (LM) on differentiation, lipid storage, and 2-deoxy-D-glucose (2DG) uptake in 3T3-L1 preadipocytes. Genes and proteins associated with differentiation, lipid accumulation, 2DG uptake and its signaling pathways in the adipocytes were analyzed using qPCR and western blot methods. LM treatment increased differentiation, lipid accumulation, and the expression of adipogenic and lipogenic markers such as C/EBP-alpha, C/EBP-beta, PPAR gamma, SREBP-1, RXR, FAS, and adiponectin. However, the LM concentration at 10 mu M decreased (p < 0.05) adipogenesis and lipogenesis via regulating key transcriptional factors. LM treatment increased activation of Akt by increasing its phosphorylation, but p44/42 activation was not altered. MK-2206, an Akt specific inhibitor, reduced the activation of Akt phosphorylation whereas LM treatment aborted the MK-2206 mediated inhibition of Akt activation. LM enhanced glucose uptake in differentiated adipocytes. Overall data suggested that LM treatment favored lipid storage and glucose uptake in adipocytes via activation of key transcriptional factors through activation of Akt phosphorylation in 3T3-L1 adipocytes.