ANTIOXIDANT POLYPHENOLS IN IMPAIRED BRAIN AND HEART FUNCTIONS ASSOCIATED WITH OBESITY AND METABOLIC DISEASES
Location: Diet, Genomics and Immunology Lab
Project Number: 1235-51000-054-00
Start Date: Mar 16, 2009
End Date: Mar 15, 2014
This project is based on the premise that many chronic diseases, including type 2 diabetes, cardiovascular diseases (CVD), and Alzheimer’s disease (AD), are strongly influenced by insulin resistance. The hypothesis is that diets that lead to improved insulin sensitivity will decrease risk factors to prevent and alleviate these diseases. We propose to evaluate the following objectives:
Objective 1: To determine the role of insulin-potentiating, antioxidant polyphenols on improved brain insulin signaling, cognitive function, and antioxidant status in rats fed a high fat, high fructose diet to induce insulin resistance and obesity.
Objective 2: To examine the mechanisms by which antioxidant polyphenols (from cinnamon, tea, coffee, and chocolate) protect neural cells from varying levels of glucose and beta-amyloid toxicity.
Objective 3: To determine the roles of these polyphenols on the renin-angiotensin system in the heart and related organs via determining their potential effects on potential mediators such as inflammatory cytokines, nitric oxide synthase, NF-kB, ACE, PPARs, serotonin receptors, and adrenoceptors.
The epidemic of insulin resistance associated with obesity, metabolic syndrome, type 2 diabetes, and cardiovascular diseases (CVD) is sweeping both developed and emerging countries. Insulin resistance has been implicated in the pathogenesis of Alzheimer’s disease (AD) and the term “type 3 diabetes” has been used to describe AD. Moreover, obesity has been recognized as an important risk factor for AD. Diets high in fat and (or) fructose contribute prominently to insulin resistance. We have recently shown in animal and human studies that cinnamon polyphenols, and related compounds, not only improve insulin function but also act as antioxidant and anti-inflammatory compounds to counteract the negative effects of insulin resistance and obesity. This proposal is designed to test the hypothesis that insulin-potentiating polyphenols from cinnamon, coffee, tea, and chocolate will alleviate insulin resistance and related diseases including CVD and AD. Insulin resistance and related pathologies will be induced by feeding rats diets high in fat and fructose. The effects of insulin potentiating polyphenols on insulin resistance, brain insulin signaling, AD-like neuropathology, cognitive function, antioxidant status, hypertension, and the renin-angiotensin system will be evaluated. Cell culture studies will also be used to elucidate the mechanisms of actions of polyphenols and related compounds derived from natural products. Verification of our hypothesis will support the use of natural products containing insulin-potentiating polyphenols, and related compounds, as important nutritional components for the prevention or decreasing risk of chronic diseases including diabetes, CVD, and AD.