Protective effect of the hydroalcoholic extract from Lampaya medicinalis Phil. (Verbenaceae) on palmitic acid- impaired insulin signaling in 3T3-L1 adipocytes

Abstract

Background: Obesity is strongly associated with insulin resistance (IR). IR at the molecular level may be defined as a diminished activation of insulin signaling-related molecules (IRS-1/Akt/AS160) as well as reduced glucose uptake. Subject with obesity have elevated plasma levels of saturated fatty acids, such as palmitic acid (PA), which triggers insulin signaling disruption in vivo and in vitro. Infusions of Lampaya medicinalis Phil. (Verbenaceae) are used in folk medicine of Northern Chile to counteract inflammatory diseases. Hydroethanolic extracts of lampaya (HEL) contain considerable amounts of flavonoids that may explain the biological activity of the plant. The aim of this study was to assess whether HEL exposure protects against PA-disrupted insulin signaling and glucose uptake in adipocytes.

Methods: Cytotoxicity of a range of HEL concentrations (0.01-10 μg/mL) was evaluated in 3T3-L1 adipocytes. Cells were exposed or not to 0.1 μg/mL of HEL before adding 0.65 mM PA or vehicle and incubated with 100 nM insulin (or vehicle) for 15 min. Phosphorylation of Tyr-IRS-1, Ser-Akt, Thr-AS160 was evaluated by Western blot. Glucose uptake was assessed using the 2-NBDG analogue.

Results: HEL was not cytotoxic at any concentration assessed. PA-induced reduction in insulin-stimulated phosphorylation of IRS-1, Akt and AS160 and glucose uptake were abolished by co-treatment with HEL.

Conclusion: These findings give new insights about the effect of HEL ameliorating PA- impaired IRS-1/Akt/AS160 pathway and glucose uptake in adipocytes. More studies should focus on lampaya, since might represent a preventive approach in individuals whose circulating PA levels contribute to IR.

Keywords: Adipocyte; Glucose uptake; Insulin signaling; Lampaya medicinalis; Palmitic acid.