Biography

     Dr. Kelley obtained a B. Sc. degree in Agriculture and Animal Husbandry, and an M. Sc. degree in Biochemistry from Punjab Agricultural University (PAU) in Ludhiana, India. He worked as a post graduate fellow at PAU for one year, where he examined the effects of dietary lipids on tissue and egg lipids in hens. Dr Kelley received his Ph. D. degree in Biochemistry in1974 from the University of Oklahoma, under the mentorship of Dr B Connor Johnson and then worked as a special consultant at the Oklahoma Medical Research Foundation for twenty months. At the Oklahoma Medical Center, Dr Kelley compared the effects of high carbohydrate and high fat diets on the regulation of hepatic lipid synthesis and the mechanisms involved. Dr Kelley worked as a research associate in the laboratory of Dr Van R Potter at McArdle Laboratory for Cancer Research, at the University of Wisconsin (UW) 1975-1980. Research conducted by Dr Kelley at UW contributed to an understanding of hormonal and nutritional regulation of amino acid transport in normal and malignant hepatocytes. Dr Kelley then served on the faculty of West Virginia University for 3 years before starting his career with the USDA, ARS, Western Human Nutrition Center as a research chemist in 1983. He served as the Research Leader for the Bioenergetics Research Unit of WHNRC from 1990-1996, and has been the Lead scientist for the project on Dietary Fat and Health at WHNRC since 1990. Within the ARS, Dr. Kelley’s area of investigation has been nutrition and immune function. He has focused on the effects of the amount and type of dietary fats on immune status, and has also examined the effects of energy intake, vitamins and minerals on immune response (IR) in collaborative studies. His research has shown that a reduction in fat intake enhanced several indices of IR in human subjects. Increased consumption of omega-6 fatty acids increased inflammatory response, while increased intake of omega-3 fatty acids decreased the production of inflammatory cytokines and eicosanoids. Most recent studies of Dr Kelley have focused on the effects of individual dietary fatty acids (docosahexaenoic acid, arachidonic acid, and conjugated linoleic acid) on risk factors for cardiovascular disease and insulin resistance, and an understanding of the mechanisms involved. He has also been interested in the health effects of phytonutrients (polyphenols and limonoids).

Research Projects

     Dr Kelley has been interested in the dietary regulation of immune and inflammatory responses. Recent research projects of Dr Kelley have focused on the effects of the amounts and types of dietary fatty acids on risk factors for cardio-vascular disease (CVD), diabetes, and other inflammatory diseases. He has also been interested in the health effects of phytonutrients (polyphenols, limonoids) and the effects of fatty acids on cell growth, differentiation and apoptosis. Dr Kelley is currently pursuing the following three research projects in addition to several other collaborations.

·        In an earlier study we had found that supplementing diets of healthy young men with normal blood lipids reduced blood triglycerides, markers of inflammation and increased HDL cholesterol. We repeated this study to examine the effects of DHA supplementation on risk factors for CVD in hypertriglyceridemic men who are at increased risk for this disease. We have completed the experimental part and sample collection phase of our second DHA study. A manuscript based on the effects of DHA on blood lipids, lipoproteins sizes and numbers is in press, AJCN. Samples and data analysis for markers of inflammation, endothelial cell function, and fatty acid composition is in progress.

·       Our second project deals with the prevention of fatty liver and insulin resistance (pre-diabetic condition) by omega-3 fatty acids. We and other investigators have previously shown that supplementing animal diets with a mixture of CLA isomers or purified t10, c12-CLA (found in margarines, shortenings, and other processed seed oils) caused fatty liver, insulin resistance, lipid peroxidation and inflammation in animal models; some of these adverse effects of t10, c12-CLA have also been found in human subjects. We recently found that concomitant supplementation of either EPA or DHA with CLA prevented the development of fatty livers, while only DHA prevented the CLA-induced insulin resistance. We are currently investigating the molecular mechanisms by which DHA prevented the development of insulin resistance in normal mice. We intend to repeat these experiments in the db/db (diabetic) mouse model to understand the role of DHA in the prevention and management of diabetes. We also plan to extend these studies to human subjects if we are able to acquire the funds needed for a human study.

·        Limonoids from citrus and other trees have been shown to have anti-inflammatory, anti-cancer and cholesterol lowering effects in animal models; health effects of citrus limonoids in humans have not been studied. In collaboration with Dr Andrew Breksa of WRRC, and Dr Susan Zunino of WHNRC, we plan to study the metabolism, safety, and health effects of  limonoids purified from citrus molasses in humans. Dr Breksa will purify the limonoids and we will study their effects on blood lipids, lipoproteins, and markers of immune and inflammatory responses in hypercholesterolemic men and women.

Research Accomplishments

·        We demonstrated that supplementing diets of hypertriglyceridemic men decreased the fasting and post-prandial triglycerides (25-30%), and it increased the HDL-cholesterol (7%). Furthermore, it reduced the numbers of total and small dense LDL particles (11 and 25%) which are considered atherogenic. It increased the concentrations of large LDL (120%) and large HDL particles (63%) which are viewed as cardio-protective. DHA also reduced the heart rate and blood pressure in these men. Overall, DHA consumption resulted in a healthy blood lipid profile.

·        We found that in addition to improving the blood lipid profile, supplementing diets of healthy men with DHA reduced the production of several markers of inflammation, including inflammatory cytokines, eicosanoids and the number of circulating granulocytes. In a separte study with healthy men, we found that supplementing their diets with arachidonic acid, an omega-6 fatty acid, increased production of inflammatory eicosanoids, B cell proliferation, and the number of circulating granulocytes. Thus, an increase in the consumption of omega-3 polyunsaturated fatty acids and a reduction in the consumption of omega-6 fatty acids may be useful in the prevention and management of inflammatory diseases.

·        We discovered that the two major isomers of CLA (c9, t11-CLA, and t10, c12-CLA) have distinct and opposite effects on the expression of several liver genes involved in lipid and fatty acid metabolism. We also, showed that only t10, c12-CLA caused the development of fatty liver and insulin resistance in the mouse model. The development of fatty liver resulted from both increased fatty acid synthesis and reduced fatty acid oxidation. While, both these isomers alter lipid metabolism, the adverse effects are mainly due to t10, c12-CLA.

·        In the mouse model, we found that concomitant supplementation with either EPA or DHA prevented the CLA-induced fatty liver, while only DHA prevented the development of insulin resistance. Increased consumption of t10, c12-CLA may be contributing to the increased incidence of diabetes and other inflammatory diseases, which may be reduced by increased intake of omega-3 fatty acids. Similar and distinct health effects of EPA and DHA should be considered to obtain specific health benefits.  

·       We demonstrated that consumption of Bing sweet cherries by healthy men and women (45 cherries/day for 28 days) decreased the concentrations of inflammatory markers (CRP, RANTES, and NO) by 18-25 %. It did not alter fasting concentrations of plasma glucose, insulin, total cholesterol, LDL and HDL cholesterol, and the numbers and size of lipoprotein particles. Cherries may thus be useful in the prevention and management of inflammatory diseases.

·        We discovered that a 50% reduction in energy intake for 12-15 weeks by overweight women markedly suppressed their immune response. Particularly striking was the decrease in the number and activity of natural killer cells that provide protection against viruses and tumor invasion. Drastic energy restriction thus may increase the risk for viral infection and tumor invasion.