Endocrine Abstracts

Background: Obesity is strongly associated with a state of chronic low grade systemic inflammation and insulin resistance (IR). IR at the molecular level may be defined as a diminished activation of the metabolic phosphatidylinositol-3-kinase (PI3K)/Akt pathway of insulin. On the other hand, inflammatory response may be activated by NF-κB. Subject with obesity have elevated plasma levels of saturated fatty acids, such as palmitic acid (PA), which triggers insulin and inflammatory signaling disruption in vivo and in vitro. Additionally, protein phosphorylation is an important regulatory mechanism to activate intracellular signaling. The protein tyrosine phosphatase 1B (PTP1B) is well known to regulate PI3K/Akt route and NF-κB inflammatory signaling. 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- induced inflammation and disruption of PI3K/Akt signaling in human adipose cells.

Methods: Cytotoxicity of a range of HEL concentrations (0.01– 10 μg/ml) was evaluated by MTS assay in in vitro differentiated adipocytes from the adipose cell line SW872. Adipocytes were incubated or not with PA for 24 h in the presence or not of HEL (2-h preincubation), and thereafter stimulated with insulin or vehicle. Thereby, experimental conditions were: control (untreated cells), 0.4 mM PA, 0.01 μg/ml of HEL, 0.01 μg/ml of HEL (2 h before) + 0.4 mM PA for 24 h, in insulin-stimulated (100 nM, 10 min) or basal conditions. Phosphorylation of Tyr-IRS-1, Ser-Akt, Ser-NF-κB and protein expression of PTP1B were evaluated by Western blot.

Results: In SW872 adipocytes, HEL was not cytotoxic at any concentration assessed. Insulin-stimulated phosphorylation of IRS-1 and Akt as well as phosphorylation of NF-κB and PTP1B protein content were not affected by treatment with 0.01 μg/ml HEL compared with vehicle-treated cells. PA-treated adipocytes showed a reduction in insulin-stimulated phosphorylation of IRS-1 and Akt compared to control (P<0.05), while the phosphorylation of NF-κB and PTP1B protein expression were elevated compared to untreated cells (P<0.05). Interestingly, these effects were prevented by HEL treatment.

Conclusion: These findings give new insights about the effect of HEL ameliorating PA- impaired insulin signaling and inflammatory markers in adipocytes. More studies should focus on lampaya, since might represent a preventive approach in individuals whose circulating PA levels contribute to inflammation and IR.