2013 Annual Report
1a.Objectives (from AD-416):
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.
1b.Approach (from AD-416):
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.
Disturbances in insulin metabolism are involved in most pathogenic processes that promote the development of chronic diseases including obesity, hypertension, diabetes, and cardiovascular diseases. One of the key components in controlling these diseases is to control the declines in insulin sensitivity associated with eating unhealthy diets. We have demonstrated that increased intake of cinnamon, high in polyphenols, improves whole body glucose, insulin, and fat metabolism. However, little is known about the effects of cinnamon polyphenols on intestinal absorption and metabolism. We demonstrated that an aqueous cinnamon extract inhibited genes coding for proinflammatory agents and stimulated anti-inflammatory factors in cells lining the rat small intestine. Cinnamon also improved genes coding for glucose and fat metabolism in these cells. These results demonstrate that cinnamon has beneficial effects on factors controlling inflammation and sugar and fat metabolism, starting at the level of absorption. We also demonstrated that an extract from chokeberry, high in polyphenols, also attenuates weight gain and modulates insulin, fat metabolism, and inflammatory factors in rats eating a high sugar diet.
Health benefits of numerous plant products are widely recognized worldwide and their major chemicals are relatively well documented. However, there is very little information regarding the potential beneficial effects of novel safflomide-type phenylpropenoic acid amides on obesity, sub-clinical inflammation and hypertension. This year, safflomide and analogues found in plant sources (e.g., coffee, cocoa, garlic, green onion, spices and herbs) were investigated in vitro and in vivo. We found safflomide to lower body weight in rats fed a high-fat and high-fructose diet. Rats supplemented with safflomide also showed increased adiponectin with reduction in visceral fat, and improved insulin resistance.
Novel-type phenolic conjugates, amkamide and derivatives, were prepared and their bioavailability was determined using an animal model, in order to validate their anti-oxidant/anti-inflammatory effects in vivo.
Three major chlorogenic acids (3,4,5-CQAs)were isolated and quantified from major instant coffee brands and their biological effects on obesity-related conditions were determined.
Qin, B., Dawson, H.D., Schoene, N.W., Polansky, M.M., Anderson, R.A. 2012. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes. European Journal of Nutrition. 28:1172-79.
Anderson, R.A., Cefalu, W.T. 2011. Chromium. In: Coates, P.M., Betz, J.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., and White, J.D., editors. Encyclopedia of Dietary Supplements, 2nd Edition, New York, N.Y.: Marcel Dekker, p. 148-156.
Park, J.B. 2012. Synthesis, biological activity, and bioavailability of moschamine, a safflomide-type phenylpropenoic acid amide found in Centaurea cyanus. Natural Product Research. 26(16):1465-72.
Anderson, R.A., Qin, B. 2011. An extract of chokeberry attenuates weight gain and modulates multiple signaling pathways in epididymal adipose tissue of rats fed a fructose-rich diet. British Journal of Nutrition. 108:581-587.