The specific aim of this proposal is to investigate potential mechanisms by which a diet high in saturated fat and refined carbohydrates (sucrose) induces insulin resistance and hypertension compared to a diet high in unrefined carbohydrate and low in fat. Hypertension afflicts one quarter of the adult population in the United States and is a hallmark risk factor for myocardial infarction, stroke and congestive heart failure. Although its cause is largely unknown, it is associated with insulin resistance/ hyperinsulinemia, oxidative stress and endothelial dysfunction. The primary hypothesis to be tested in this grant is that a high-fat, refined carbohydrate diet (HFS) increases the production of reactive oxygen/nitrogen species (e.g. ONOO-), contributing to insulin resistance, as well as sequestrating and inactivating NO leading to hypertension. To test this hypothesis, male and female rats will be raised on either the HFS or a low-fat, complex carbohydrate diet (LFCC) and blood pressure will be measured via the tail-cuff and telemetry methods. Isolated arterial segments will be used to test endothelial function. Plasma/urinary measurements will assess NO metabotites, MDA and cGMP levels. Biochemical studies will be. conducted on several tissues, including aorta, heart and kidney to measure eNOS, iNOS, nNOS and SOD proteins, NOS and SOD activities, nitrotyrosine formation and tissue cGMP levels. Studies will also be conducted to investigate the value of dietary modification (switching to an LFCC diet or antioxidant supplementation) and exercise training for controlling hypertension, as well as the role of caloric restriction on the development of hypertension. The results of these studies may provide a mechanism to explain how HFS type diets cause insulin resistance and hypertension, and how a LFCC diet, antioxidant therapy or exercise training aid in the control of insulin resistance and hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL068406-01
Application #
6406389
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Schucker, Beth
Project Start
2001-09-30
Project End
Budget Start
2001-09-30
Budget End
2002-09-29
Support Year
1
Fiscal Year
2001
Total Cost
$40,196
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Roberts, Christian K; Ng, Carey; Hama, Susan et al. (2006) Effect of a short-term diet and exercise intervention on inflammatory/anti-inflammatory properties of HDL in overweight/obese men with cardiovascular risk factors. J Appl Physiol 101:1727-32
Sonkusare, Swapnil; Fraer, Mony; Marsh, James D et al. (2006) Disrupting calcium channel expression to lower blood pressure: new targeting of a well-known channel. Mol Interv 6:304-10
Sindhu, Ram K; Koo, Ja-Ryung; Sindhu, Kunal K et al. (2006) Differential regulation of hepatic cytochrome P450 monooxygenases in streptozotocin-induced diabetic rats. Free Radic Res 40:921-8
Roberts, Christian K; Won, Dean; Pruthi, Sandeep et al. (2006) Effect of a diet and exercise intervention on oxidative stress, inflammation and monocyte adhesion in diabetic men. Diabetes Res Clin Pract 73:249-59
Roberts, Christian K; Barnard, R James; Sindhu, Ram K et al. (2006) Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome. Metabolism 55:928-34
Roberts, Christian K; Won, Dean; Pruthi, Sandeep et al. (2006) Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors. J Appl Physiol 100:1657-65
Chen, Andrew K; Roberts, Christian K; Barnard, R James (2006) Effect of a short-term diet and exercise intervention on metabolic syndrome in overweight children. Metabolism 55:871-8
Roberts, Christian K; Barnard, R James (2005) Effects of exercise and diet on chronic disease. J Appl Physiol 98:3-30
Sindhu, Ram K; Roberts, Christian K; Ehdaie, Ashkan et al. (2005) Effects of aortic coarctation on aortic antioxidant enzymes and NADPH oxidase protein expression. Life Sci 76:945-53
Roberts, Christian K; Barnard, R James; Sindhu, Ram K et al. (2005) A high-fat, refined-carbohydrate diet induces endothelial dysfunction and oxidant/antioxidant imbalance and depresses NOS protein expression. J Appl Physiol 98:203-10

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