Degrees

Ph.D., Biochemistry, Oklahoma University, OK, 1974

M.Sc., Biochemistry, Punjab Agric. University, India, 1969

B.Sc., Agric. & A.H.,   Punjab Agric. University, India, 1967

Research Interests

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.

Professional Societies

American Society for Nutritional Sciences

International Scientific Society for Fatty Acids and Lipids

British Nutrition Society

Graduate Group Affiliation

Department of Nutrition, University of California, Davis

Research Journal Editorial Assignments

Journal of Nutrition, Member Editorial Board, 2007-present

British Journal of Nutrition, First Editor, 2008-present.

Lipids, Associate Editor, 2001-present

Nutrition Research, Consulting Editor, 1993-present

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 that will reduce the risk for cardiovascular disease.

·           In addition to improving the blood lipid profile, supplementing diets of healthy and of hypertriglyceridemic men with DHA reduced the ex-vivo production of inflammatory cytokines and eicosanoids; it also decreased circulating concentration of inflammatory markers including CRP, IL-6, GM-CSF, and the number of granulocytes. In contrast to the anti-inflammatory effects of DHA, supplementation with arachidonic acid, an omega-6 fatty acid, increased production of inflammatory eicosanoids, B cell proliferation, and the number of circulating granulocytes. Thus, both an increase in the consumption of omega-3 polyunsaturated fatty acids and a reduction in the consumption of omega-6 fatty acids are needed for 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. Adverse effects of CLA and other trans fatty acids (TFA) have also been found in human subjects. An estimated 30-40% of US adults have fatty liver and insulin resistance; a reduction in the intake of CLA and other TFA will help reduce the epidemics of these metabolic disorders.

·           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) from flaxseed oil completely prevented the CLA-induced insulin resistance and partially prevented the increase in liver fat. Consumption of t10, c12-CLA and other trans fatty acids is one of the major factors contributing to the increased incidence of diabetes and other inflammatory diseases; these effects can be reduced by increased intake of omega-3 fatty acids. ALA, EPA, and DHA all provide health benefits, yet they vary in their efficacy and 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.

Kelley Research Lab

Yuriko Adkins, Ph.D.                 Nutritional Molecular Biologist

Dr. Adkins received her Ph.D. and completed her postdoctoral training at the University of California, Davis, then worked in the biotechnology industry as a scientific consultant in the area of therapeutic concepts for health and disease prevention.   She currently investigates the mechanisms by which dietary omega-3 fatty acids as well as phytonutrients decrease the risk for diabetes and cardiovascular disease through the modulation of inflammatory signaling pathways.  She utilizes molecular and biochemical methodologies including analysis of tissue lipids and fatty acids using gas chromatography mass spectrometry (GC-MS) and gene and protein expression studies.   She also has extensive experience in isolation and purification of proteins, cell-ligand uptake and transport studies, and preclinical evaluation of protein bioactivity and stability.  

Dawn Fedor                               Ph.D. Student, Graduate Group of Nutritional Biology

Dawn is studying the effects of omega-3 fatty acids on insulin resistance and inflammation. Her research objectives include determining the effectiveness of individual fatty acids in the prevention and reversal of insulin resistance and nonalcoholic fatty liver disease in an animal model. She will be examining the molecular mechanisms through which fatty acids regulate immune and inflammatory responses using molecular and biochemical techniques such as lipid analysis of plasma and tissue samples using GC-MS.

Divya Denduluri                         Ph.D. Student, Graduate Group of Nutritional Biology

Extramural Collaborators     

Kevin Dawson, M.D.	Senior Informatics Scientist, Department of Molecular and Cellular Biology, University of California, Davis, CA
Fawaz G. Haj, Ph.D.	Assistant Professor, Department of Nutrition, University of California, Davis, CA
Andrew Breksa, Ph.D.	Research Chemist, Western Regional Research Center, USDA, Albany, CA.
Bruce E. Mackey, Ph.D.	Consulting Statistician, Western Regional Research Center, USDA, Albany, CA
Manabu T. Nakamura, Ph.D.	Associate Professor of Nutrition, Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, IL
Stephen Griffey, DVM, Ph.D.	Clinical Professor, Director of the Comparative Pathology Laboratory, University of California, Davis, CA
Ajit K. Verma, Ph.D.	Professor of Oncology, University of Wisconsin, Madison, WI
David Siegel, M.D.   Raymond  Rodriguez, Ph.D.     JaiPal Singh, Ph.D.	Director, Mather VA Medical Center, Sacramento, CA   Professor Molecular and Cellular Biology, Director  Center of Excellence in Nutritional Genomics, UCD    Chief Scientific Officer & Vice President of Research, Saint Joseph’s Translational Research Institute, Atlanta, Ga.

Intramural Collaborators

Charles Stephensen, Ph.D.	Research Leader
Daniel Hwang, Ph.D.	Research Molecular Biologist
Susan Zunino, Ph.D.	Research Molecular Biologist

Recent Publications  

1.          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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18710604

2.          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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19158225

3.          Fedor D, Kelley DS. Prevention of insulin resistance by n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care. 2009;12:138-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19202385

4.          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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18156400

5.          Fedor D, Gill SH, Adkins Y, Kelley DS. Dietary Supplementation With Omega-3 Fatty Acids: Can It Reduce Insulin Resistance? Clinical Nutrition Insights. 2008;34:1-4.

6.          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. Metab Syndr Relat Disord. 2007;5:315-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18370801

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

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

9.          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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17217560

10.        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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17684201

11.        Stephensen CB, Kelley DS. The innate immune system: friend and foe. Am J Clin Nutr. 2006;83:187-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16469973

12.        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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16549461

13.        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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16631360

14.        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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16263429

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

16.        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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15159234

17.        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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15134140

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

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

 

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