Insulin resistance in 3T3-L1 adipocytes by TNF-α is improved by punicic acid through upregulation of insulin signalling pathway and endocrine function, and downregulation of proinflammatory cytokines

Abstract

Insulin resistance (IR) has become a major threat to public health due to its role in metabolic syndrome. Inflammation associated with IR is an interesting area of biomedical research in recent years and is expected to affect insulin signalling pathway via downregulating glucose transporters. In the present study, we evaluate the potential of punicic acid (PA), a nutraceutical found in pomegranate seed oil, against TNF-α induced alteration in 3T3-L1 adipocytes on glucose metabolism, endocrine function and inflammation. IR was induced in 3T3-L1 adipocytes by treating with TNF-α (10 ng/mL) and various concentrations of PA (5, 10, 30 μM) were incubated simultaneously. After 24 h, we found that TNF-α treatment increased mRNA expression of SOCS3, PTP1B and a decrease in IRS1 causing diminished glucose uptake. Further, it showed significantly increased transcriptional activity of NFκB and leptin secretion while PA maintained leptin levels normal. Additionally, PA prevented the over-expression of phosphorylated JNK in a dose dependent manner during IR. PA also ameliorated significantly the upregulation of proinflammatory cytokines. From the results, we conclude that PA is effective to ameliorate TNF-α induced IR and also we recommend the intake of PA for control and management of IR and its associated complications.