Insulin Sensitivity of Adipocytes is Improved by Pomegranate Mesocarp Through Reduced Oxidative Stress and Inflammation.

Objective: Inflammatory phenomena and increase in oxidative stress in cell physiopathology progression render therapeutic strategies based on nutritional antioxidants necessary. It was thus aimed at assessing the effectiveness of the pomegranate mesocarp extract (PME) on differentiation of preadipocytes to adipocytes in the presence/absence of hydrogen peroxide (H₂O₂), a model mimicking insulin resistance.

Method: The effect of PME on lipid accumulation, protein expression of antioxidant, inflammatory and adipogenic biomarkers, reactive oxygen species production, activity of antioxidant enzymes and secretion of IL-6 has been evaluated during the differentiation of preadipocytes to adipocytes, in the presence or absence of H₂O₂.

Results: H₂O₂ reduced the expression of the regulator of insulin sensitivity PPARγ and suppressed adipocyte differentiation. PME counteracted the effect of H₂O₂. The latter induced a higher level of fat accumulation by promoting the expressions of the adipogenic markers PPARγ, C/EBPα, FABP4 and CD36 as compared to the control and the H₂O₂-treated differentiating cells. During the progression of adipogenesis, highest increase (p < 0.05) in IL-6 secretion, by 3.16 and 3.85 folds, was observed on day 2 of differentiation in control and H₂O₂-treated cells, respectively, compared to day 0. PME significantly decreased (p < 0.01) the secretion of the cytokine in addition to suppressing the expression of NFκB. PME also prevented the reduction of superoxide dismutase, catalase and glutathione peroxidase activities that occurred during adipogenesis, by at most 33%, 119% and 42%, respectively.

Conclusion: These findings indicate that PME efficiently improves insulin sensitivity and can significantly counteract oxidative stress and inflammation.