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United States Department of Agriculture

Agricultural Research Service

DARSHAN S. KELLEY

Research Chemist

 

 

Ph.D., Biochemistry

Oklahoma University, OK

 

 

Office:  University of California, Davis

             430 West Health Sciences Drive

             Davis, CA 95616

 

Phone: (530) 752-5138

 

Fax:     (530) 752-5271

 

 

Kelley Lab

                                                                                                                                   

    

 

 

Biography

 

Dr. Kelley obtained an M. Sc. degree in Biochemistry from Punjab Agricultural University in Ludhiana, India and then received his Ph. D. degree in Biochemistry in 1974 from the University of Oklahoma, under the mentorship of Dr B Connor Johnson. Here, he compared the effects of high fat and high carbohydrate 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 Research Center (WHNRC) as a research chemist in 1983. He served as the Research Leader for the Bioenergetics Research Unit from 1990-1996, and as the Lead Scientist for the project on Dietary Fat and Health from 1990-2008. In addition to his current employment with ARS, Dr. Kelley is an adjunct professor in the Department of Nutrition at University of California Davis since 1999.  His research has focused not only on the effects of the amount and type of dietary fats on immune status, but also examined the effects of energy intake, vitamins and minerals on immune response. His current studies encompasses the effect of individual dietary fatty acids (docosahexaenoic acid, arachidonic acid, and conjugated linoleic acid, a trans fat) on risk factors for cardiovascular disease and insulin resistance, and understanding the molecular mechanisms involved.  In addition, Dr Kelley investigates the health effects of phytonutrients (polyphenols and limonoids).

Research Program

Dr Kelley’s expertise is in the dietary regulation of immune and inflammatory responses. Recent research projects have focused on the effects of amounts and types of dietary fatty acids on risk factors for cardiovascular disease (CVD), diabetes, and other inflammatory diseases. He also investigates the health effects of phytonutrients (polyphenols and limonoids). Dr Kelley is currently pursuing three research projects in addition to several other collaborations:

 

1)      Effects of doxosahexaenoic acid (DHA) supplementation on risk factors for CVD in hypertriglyceridemic men.

2)      Effects of citrus limonoids on blood lipids and markers of inflammation in hypercholesterolemic men and women.

3)      Role of dietary fatty acids in the development and prevention of fatty liver and insulin resistance in the mouse model.

Research Accomplishments

·          We demonstrated that supplementing diets of hypertriglyceridemic men with DHA decreased fasting and post-prandial triglycerides (25-30%), and increased the HDL-cholesterol (7%). Furthermore, it reduced the numbers of total and small dense LDL particles (11 and 25%) which are considered atherogenic, and increased the concentrations of large LDL (120%) and large HDL particles (63%) which are viewed as cardio-protective. DHA also reduced the number of circulating remnant chylomicron particles, 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, while supplementing men 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. Adverse effects of CLA have also been found in human subjects. 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. Alpha linolenic acid (ALA) completely prevented the CLA-induced insulin resistance and partially prevented the increase in liver fat. Increased consumption of t10, c12-CLA and other trans fatty acids 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, DHA, and ALA 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 %. 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.

 

Selected Articles & Patent Applications

1.            Kelley, DS, Adkins Y, Woodhouse LR, Swislocki A, Mackey BE, Siegel D. Docosahexaenoic Acid Supplementation Improved Lipocentric but Not Glucocentric Markers of Insulin Sensitivity in Hypertriglyceridemic men. Metabolic Syndrome and Related Disorders 10:32-38, 2012.

 

2.              Dawson K, Zhao L, Adkins Y, Vemuri M, Rodriguez RL, Gregg JP, Kelley DS, Hwang D. Modulation of Blood Cell Gene Expression by DHA Supplementation in Hypertriglyceridemic Men. J Nutr. Biochem. 2011, Jul 18, Epub ahead of print.

 

3.            Zunino SJ, Parelman MA, Freytag TL, Stephensen CB, Kelley DS, Mackey BE, Woodhouse LR, Bonnel EL. Effects of Dietary Strawberry Powder on Blood Lipids and Inflammatory Markers in Obese Humans. British Journal of Nutrition, 2011 Nov 9:1-10 [Epub ahead of print].

 

4.            Fedor D, Adkins Y, Mackey B, Kelley DS. Docosahexaenoic Acid Prevents trans 10, c12-Conjugated Linoleic Acid-Induced Non-Alcoholic Fatty Liver Disease in Mice by Altering Expression of Hepatic Genes Regulating Fatty Acid Synthesis and Oxidation. Metabolic Syndrome and Related Disorders, accepted for publication November 2011.

 

5.     Stephensen CB, Armstrong P, Newman JP, Pedersen TL, Legault J, Schuster GU, Kelley DS, Vikman S, Hartiala J, Nassir R, Seldin MF, Allayee H. ALOX5 gene variants affect eicosanoid production and response to fish oil supplementation. J Lipid Res. 52: 991-1003, 2011

 

6.            Adkins Y, Kelley DS. Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids. J Nutr Biochem. 2010;21:781-92.

 

7.            Fedor D, Kelley DS. Prevention of insulin resistance by n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care. 2009;12:138-46.

 

8.            Kelley DS, Siegel D, Fedor DM, Adkins Y, Mackey BE. DHA supplementation decreases Serum C-reactive protein and other markers of inflammation in hypertriglyceridemic men. J Nutr. 2009;139:495-501.

 

9.            Kelley DS, Vemuri M, Adkins Y, Gill SH, Fedor D, Mackey BE. Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin resistance in mice. Br J Nutr. 2009;101:701-8.

 

10.         Fedor D, Gill SHS, Adkins Y, Kelley DS. Dietary supplementation with omega-3 fatty acids: can it reduce insulin resistance? Clinical Nutrition Insight. 2008;34:1-4.

 

11.         Kelley DS, Siegel D, Vemuri M, Chung GH, Mackey BE. Docosahexaenoic acid supplementation decreases remnant-like particle-cholesterol and increases the (n-3) index in hypertriglyceridemic men. J Nutr. 2008;138:30-5.

 

12.         Kelley DS, Siegel D, Vemuri M, Mackey BE. Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men. Am J Clin Nutr. 2007;86:324-33.

 

13.         Rasooly R, Kelley DS, Greg J, Mackey BE. Dietary trans 10, cis 12-conjugated linoleic acid reduces the expression of fatty acid oxidation and drug detoxification enzymes in mouse liver. Br J Nutr. 2007;97:58-66.

 

14.         Vemuri M, Kelley DS. Effect of dietary fatty acids on lipid metabolism. In: Chow CK, editor. Fatty Acids in Foods and Their Health Implications. 3rd ed. Boca Raton: CRC Press; 2007. p. 591-630.

 

15.         Vemuri M, Kelley DS, Erickson KL. Health effects of foods rich in polyphenols. In: De Meester F, Watson RR, editors. Wild-Type Food in Health Promotion and Disease Prevention; The Columbus Concept: Humana Press; 2007. p. 393-412.

 

16.         Vemuri M, Kelley DS, Mackey BE, Rasooly R, Bartolini G. Docosahexaenoic acid (DHA) but not eicosapentaenoic acid (EPA) prevents trans-10, cis-12 conjugated linoleic acid (CLA)-induced insulin resistance in mice. Metabol Syndr and Related Dis. 2007;5:315-22.

 

17.         Kelley DS, Bartolini GL, Newman JW, Vemuri M, Mackey BE. Fatty acid composition of liver, adipose tissue, spleen, and heart of mice fed diets containing t10, c12-, and c9, t11-conjugated linoleic acid. Prostaglandins Leukot Essent Fatty Acids. 2006;74:331-8.

 

18.         Kelley DS, Rasooly R, Jacob RA, Kader AA, Mackey BE. Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women. J Nutr. 2006;136:981-6.

 

19.         Stephensen CB, Kelley DS. The innate immune system: friend and foe. Am J Clin Nutr. 2006;83:187-8.

 

20.         Erickson KL, Kelley DS, Hubbard NE. Dietary Fat, and Immunity in Humans. In: Gershwin ME, Nestel P, Keen CL, editors. Handbook of Nutrition and Immunity. Totowa, NJ: Humana Press; 2005.

 

21.         Kelley DS, Hubbard NE, Erickson KL. Regulation of human immune and inflammatory responses by dietary Fatty acids. Adv Food Nutr Res. 2005;50:101-38.

 

 

22.         Erickson KL, Kelley DS, Hubbard NE. Dietary Fat, Immunity, and Cancer. In: Hughes DA, Darlington LG, Bendich A, editors. Diet and Immune Functions. Totowa, NJ: Humana Press; 2004. p. 345-60.

 

23.         Hubbard NE, Kelley DS, Erickson KL. Effects of Dietary Conjugated Linoleic Acid on Immune Functions and Cancer. In: Chandra RK, editor. Nutrition and Immunology for 21st Century Toronto: TSAR Health; 2004. p. 83-99.

 

24.         Kelley DS, Bartolini GL, Warren JM, Simon VA, Mackey BE, Erickson KL. Contrasting effects of t10,c12- and c9,t11-conjugated linoleic acid isomers on the fatty acid profiles of mouse liver lipids. Lipids. 2004;39:135-41.

 

25.         Turnlund JR, Jacob RA, Keen CL, Strain JJ, Kelley DS, Domek JM, Keyes WR, Ensunsa JL, Lykkesfeldt J, Coulter J. Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men. Am J Clin Nutr. 2004;79:1037-44.

 

26.         Warren JM, Simon VA, Bartolini G, Erickson KL, Mackey BE, Kelley DS. Trans-10,cis-12 CLA increases liver and decreases adipose tissue lipids in mice: possible roles of specific lipid metabolism genes. Lipids. 2003;38:497-504.

 

27.         Kelley DS, Simon VA, Taylor PC, Rudolph IL, Benito P, Nelson GJ, Mackey BE, Erickson KL. Dietary supplementation with conjugated linoleic acid increased its concentration in human peripheral blood mononuclear cells, but did not alter their function. Lipids. 2001;36:669-74.

 

 

28.         Medina EA, Horn WF, Keim NL, Havel PJ, Benito P, Kelley DS, Nelson GJ, Erickson KL. Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Lipids. 2000;35:783-8.

 

29.         Kelley DS, Taylor PC, Nelson GJ, Mackey BE. Dietary docosahexaenoic acid and immunocompetence in young healthy men. Lipids. 1998;33:559-66.

 

 

30.         Kelley DS, Taylor PC, Nelson GJ, Mackey BE. Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men. Lipids. 1998;33:125-30.

 

31.         Kelley DS, Taylor PC, Nelson GJ, Schmidt PC, Mackey BE, Kyle D. Effects of dietary arachidonic acid on human immune response. Lipids. 1997;32:449-56.

 

32.         Kelley DS, Daudu PA, Branch LB, Johnson HL, Taylor PC, Mackey B. Energy restriction decreases number of circulating natural killer cells and serum levels of immunoglobulins in overweight women. Eur J Clin Nutr. 1994;48:9-18.

 

33.         Kelley DS, Dougherty RM, Branch LB, Taylor PC, Iacono JM. Concentration of dietary N-6 polyunsaturated fatty acids and the human immune status. Clin Immunol Immunopathol. 1992;62:240-4.

 

34.         Kelley DS, Branch LB, Love JE, Taylor PC, Rivera YM, Iacono JM. Dietary alpha-linolenic acid and immunocompetence in humans. Am J Clin Nutr. 1991;53:40-6.

 

35.         Kelley DS, Nelson GJ, Serrato CM, Schmidt PC, Branch LB. Effects of type of dietary fat on indices of immune status of rabbits. J Nutr. 1988;118:1376-84.

 

36.         Kelley DS, Kletzien RF. Ethanol modulation of the hormonal and nutritional regulation of glucose 6-phosphate dehydrogenase activity in primary cultures of rat hepatocytes. Biochem J. 1984;217:543-9.

 

37.         Kelley DS, Evanson T, Potter VR. Calcium-dependent hormonal regulation of amino acid transport and cyclic AMP accumulation in rat hepatocyte monolayer cultures. Proc Natl Acad Sci U S A. 1980;77:5953-7.

 

38.         Kelley DS, Becker JE, Potter VR. Effect of insulin, dexamethasone, and glucagon on the amino acid transport ability of four rat hepatoma cell lines and rat hepatocytes in culture. Cancer Res. 1978;38:4591-600.

 

Book Chapters

1.    Kelley, D.S., Branch, L.B., Love, J.E., Taylor, P.C., Rivera, Y.M. and Iacono, J.M.   Dietary Alpha-Linolenic Acid and Immunocompetence in Humans.  Am. J. Clin. Nutr. 53:40-6. 1991.

 

2.    Kelley, D.S., Serrato, C.M., Taylor, P.C. and Rivera, Y.M.    Effect of Calcium on the Isolation and in vitro Proliferation on Rabbit Peripheral Blood Mononuclear Cells.  Amer. Lab 10:18-20.  1991.

 

3.    Burri, B.J., Dougherty, R.M., Kelley, D.S., Iacono, J.M. Platelet Aggregation in Humans is Affected by Replacement of Dietary Linolenic Acid with Oleic Acid.  Am. J. Clin. Nutr. 54:359-62. 1991.

 

 

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