Kelley Lab

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.

 

RESEARCH TEAM

 

Yuriko Adkins, Ph.D.   Nutritional Molecular Biologist

Dr. Adkins received her Ph.D. at the University of California, Davis. She completed a research fellowship at the National Cancer Institute/National Institutes of Health and previously worked in the biotechnology industry as a scientific consultant in therapeutic concept for health and disease. She currently investigates the mechanisms by which dietary omega-3 fatty acids as well as phytonutrients decrease the risk for developing metabolic syndrome, including cardiovascular disease, through the modulation of inflammatory signaling pathways. She has extensive molecular and biochemical experience including quantification of fatty acids in tissues and experimental diets using gas chromatography mass spectrometry (GC-MS), gene expression studies, expression of recombinant human proteins, isolation and purification of proteins using fast protein liquid chromatography (FPLC), preclinical evaluation of protein bioactivity and stability for therapeutic potential for health related conditions, and cell-ligand binding, uptake, and transport studies.

 

Dawn Fedor                   Ph.D. Candidate, UC Davis Graduate Group of Nutritional Biology

Dawn is studying the effects of omega-3 fatty acids on insulin resistance and inflammation. Her current 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 including lipid analysis (GC-MS) of plasma and tissues.

Divya Denduluri            M.S. Student, UC Davis Graduate Group of Nutritional Biology

 

Shannon Householder UC Davis Intern, Nutritional Biochemistry, Pre-Med

 

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.

 

RECENT PUBLICATIONS (selected)

1. Fedor D, Adkins Y, Newman JW, Mackey B, Kelley DS. The Effect of Docosahexaenoic Acid on t10, c12-Conjugated Linoleic Acid-Induced Changes in Fatty Acid Composition of Mouse Liver, Adipose and Muscle. Metabolic Syndrome and Related Disorders, 2013, 11:63-70
2. Kelley DS. Adkins Y, Reddy A, Woodhouse LR, Mackey BE, Erickson KL. Sweet Bing Cherries Lower Circulating Concentrations of Markers for Chronic Inflammatory Diseases in Healthy Human Subjects. Journal of Nutrition, 2013, 143:340-344.
3. Adkins Y, Schie IW, Fedor D, Reddy A, Nguyen S, Zhou P, Kelley DS, Wu J. A Novel Model of Nonalcoholic Steatohepatitis with Significant Insulin Resistance. Laboratory Investigation, 2013, 93:1313-1322.
4. Schuster GU, Bratt JM, Jiang X, Pedersen TL, Grapov D, Adkins Y, Kelley DS, Newman JW, Kenyon NJ, Stephensen CB. Dietary Long-Chain Omega-3 Fatty Acids do not Diminish Eosinophilic Inflammation in Mice. Am J Respir Cell Mol Biol. 50:626-636, 2014.
5. Schiri M., Adkins Y., Ishida N., Umeno A., Shigeri Y., Yoshida Y., Fedor D.M., Mackey, and Kelley D.S. DHA concentration of Red Blood Cells is 1 inversely associated with markers of lipid peroxidation in men taking DHA supplement. Jour. Clin. Biochem and Nutr. 55: 196-202, 2014.
6. Kelley, D.S., Adkins Y., Zunino, S. J., Woodhouse, L. R., Bonnel, E. L., Breksa, A.P., Manners, G.D., Mackey, B.M. Citrus limonin glucoside supplementation decreased biomarkers of liver disease in overweight human subjects. J. Func. Foods. 12:217-281, 2015.
7. Kelley, D.S. Purified limonin glucoside for prevention and treatment of chronic diseases. US Patent # 9,066,965 B1, issued on 06/30/2015.
8. Adkins Y., Fedor D. M., Mackey B. E., Wu J., and Kelley D. S. Dietary docosahexaenoic acid reverses nonalcoholic steatohepatitis and fibrosis caused by conjugated linoleic acid supplementation in mice. J. Func. Foods. 20:443-452, 2016.
9. Zunino SJ, Storms DH, Freytag TL, Adkins Y, Bonnel E. L, Woodhouse L. R, Breksa A. P, Manners G. D, Mackey BE, Kelley D. S. Dietary supplementation with purified citrus limonin glucoside does not alter ex vivo functions of circulating T lymphocytes or monocytes in overweight/obese human adults. Nutr. Res 36: 24-30, 2016.
10. Vemuri M, Adkins Y, Mackey BE, Kelley D. S. Docosahexaenoic acid and eicosapentaenoic acid did not alter trans-10, cis-12 conjugated linoleic acid incorporation into mice brain and eye lipids. Lipids, 2017, DOI 10.1007/s11745-017-4282-x
11. Laugero KD, Adkins Y, Mackey BE, Kelley DS. Emotion-based cognition in mice is differently influenced by dose and chemical form of dietary docosahexaenoic acid. Nutrients, 2017, 9:993, doi:10.3390/nu9090993.