Effect of Alpha-Phellandrene on Glucose Uptake and Adipogenesis in Insulin Resistant 3T3-L1 Adipocytes: an in vitro and in silico Approach

Abstract

Aim: The present study was designed to investigate the effect of alpha-phellandrene, a monoterpene present in essential oils of mint, turmeric, black pepper, and cinnamon, on adipocyte function under insulin-resistant conditions.Materials and Methods: Mature 3T3-L1 adipocytes were exposed to high glucose (25 mM) and 0.6 nM/L of insulin for 24 hr to convert to IR-3T3-L1 adipocytes. The adipocytes were grouped into group 1: normal control, group 2: diabetic control, group 3: diabetic group treated with alpha-phellandrene (65 μM), and group 4: diabetic group treated with rosiglitazone (0.1 μM). Glucose uptake assay, triglyceride accumulation, and the activity of glycerol-3-phosphate dehydrogenase were measured. The binding affinity of alpha-phellandrene with PPARγ and SREBP-1c was analyzed by docking studies using AutoDock Vina (V. 4.0) in Pyrx software.Results: Glucose uptake, triglyceride accumulation, and activity of glycerol-3-phosphate dehydrogenase were found to be decreased in the diabetic control compared to the normal control group. Alpha-phellandrene at a dose of 65 μM increased glucose uptake, enhanced glycerol-3-phosphate activity, and triglyceride accumulation in adipocytes, which were found to be comparable with the standard drug rosiglitazone. A high binding affinity of alpha-phellandrene with key transcription factors, PPARγ and SREBP-1c, which are associated with adipogenesis and steroidogenesis, was observed in molecular docking studies.Conclusion: These results suggest that alpha-phellandrene positively regulates adipocyte function and ameliorates dyslipidemia and hyperglycemia in type II diabetes mellitus.

Keywords: 3T3-L1 adipocytes; Alpha-phellandrene; Glucose uptake; PPARγ; SREBP-1c