Drug Discov Ther. 2008;2(4):254-261.

The effects of dietary obesity on protein expressions of insulin signaling pathway in rat aorta.

Fatani SH, Naderali EK, Panchiani S, Shah F, Wong C


The deleterious effects of obesity on insulin response in vasculature may be due to changes in various components of insulin signaling pathway. Therefore, this study was designed to investigate effects of dietary-obesity, removal of palatable diet, and fenofibrate treatment on protein expressions of insulin signaling pathway in rat aorta. Adult male Wistar rats were fed either standard chow or a palatable diet (untreated obese animals) for 15 weeks. Another group of rats were fed the palatable diet for 8 weeks followed by standard chow for further 7 weeks, while a further group were fed the palatable diet for 15 weeks and were dosed with fenofibrate (50 mg/kg/day) for the last 7 weeks. Untreated obese animals had significantly higher body weight than other three groups (p < 0.05 for all). There were no significant differences between IR-β, IRS1 and IRS2, Akt, Shc, and ERK1/2 levels in chow-fed and untreated obese animals, while PI 3-kinase level were significantly (p < 0.0001) decreased in untreated obese animals. Chronic removal of palatable diet completely reversed the levels of PI 3-kinase to the normal while, fenofibrate treatment further reduced PI 3-kinase levels. On the other hand, there was a significant (p < 0.05) increase in eNOS in untreated obese animals compared with chow-fed controls. This effect was reversed by removal of palatable diet and fenofibrate treatment. These data suggest that dietary-obesity selectively inhibits PI 3-kinase while, removal of obesity-inducing diet improves PI 3-kinase levels which may have a role in vascular reactivity.

KEYWORDS: Obesity, Insulin resistance, Insulin signaling pathway, Vascular function, PI 3-kinase, Fenofibrate

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