Restoration of the adipogenic gene expression by naringenin and naringin in 3T3-L1 adipocytes
Lakshi A. Dayarathne, Sachithra S. Ranaweera, Premkumar Natraj, Priyanka Rajan, Young Jae Lee, Chang‐Hoon Han
Abstract
Background: Naringenin and its glycoside naringin are well known citrus flavonoids with several therapeutic benefits.Although the anti-adipogenic effects of naringenin and naringin have been reported previously, the detailed mechanism underlying their anti-adipogenesis effects is poorly understood.Objectives: This study examined the anti-adipogenic effects of naringenin and naringin by determining differential gene expression patterns in these flavonoids-treated 3T3-L1 adipocytes.Methods: Lipid accumulation and triglyceride (TG) content were determined by Oil red O staining and TG assay.Glucose uptake was measured using a 2-[N-(7-Nitrobenz-2-oxa-1,3diazol-4-yl)amino]-2-deoxy-d-glucose fluorescent d-glucose analog.The phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl Co-A carboxylase (ACC) were observed via Western blot analysis.Differential gene expressions in 3T3-L1 adipocytes were evaluated via RNA sequencing analysis.Results: Naringenin and naringin inhibited both lipid accumulation and TG content, increased phosphorylation levels of both AMPK and ACC and decreased the expression level of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in 3T3-L1 adipocytes.RNA sequencing analysis revealed that 32 up-regulated (> 2-fold) and 17 down-regulated (< 0.6-fold) genes related to lipid metabolism, including Acaca, Fasn, Scd1, Mogat1, Dgat, Lipin1, Cpt1a, and Lepr, were normalized to the control level in naringenin-treated adipocytes.In addition, 25 up-regulated (> 2-fold) and 25 down-regulated (< 0.6-fold) genes related to lipid metabolism, including Acaca, Fasn, Fabp5, Scd1, Srebf1, Hmgcs1, Cpt1c, Lepr, and Lrp1, were normalized to the control level by naringin. Conclusions:The results indicate that naringenin and naringin have anti-adipogenic potentials that are achieved by normalizing the expression levels of lipid metabolism-related genes that were perturbed in differentiated 3T3-L1 cells.