Bruce Hammock and Angela Zivkovic.

DAVIS--A two-year pilot research grant awarded to the Bruce Hammock laboratory at UC Davis may determine if omega 3-fatty acids, commonly found in fish oils, can help reverse a chronic inflammatory disease of the kidneys.

Collaborating on the multidisciplinary project are researcher and grant author Angela Zivkovic of the Hammock lab;  principal investigator Hammock, professor in the Department of Entomology; biochemist and food scientist Bruce German, professor in the Department of Food Science and Technology; and clinician and cell biologist Robert Weiss, professor in the Division of  Nephrology, Department of Internal Medicine, School of Medicine.

 “In more than 30 percent of IgAN patients, the disease progresses to end-stage kidney disease, resulting in hemodialysis and kidney transplant,” Zivkovic said. “The disease is not well understood, and there are no proven treatments.” 

The $84,000 multi-disciplinary grant, “Development of a Metabolic Assessment Tool for Chronic Kidney Disease,” is funded by the UC Davis Center for Health and Nutrition Research. The work involves substances that make up omega-3 acids.

“Signaling lipids, or eicosanoids, are derived from essential fatty acids, which include omega-3 and omega-6 fatty acids,” Zivkovic said. “These fatty acids are essential because they cannot be synthesized in the body, and therefore need to be obtained from the diet. Whereas omega-6 fatty acids are abundant in the western diet in the form of grains and cooking oils, long-chain omega-3 fatty acids can be obtained only from marine sources. Fish oil is an excellent source of omega-3 fatty acids, and it has been shown to improve kidney function in animal studies but in human trials show inconsistency.”

Zivkovic said preliminary evidence shows that IgAN patients have deficiencies in omega-3 fatty acids.  

“In some IgAN patients, omega-3 fatty acids help reverse kidney disease and improve kidney function, in other patients, there is no benefit, and the reason for this inconsistency is unclear,” she said.

The researchers hope to learn whether certain IgAN patients have metabolic disturbances in omega-3 fatty acid metabolism that play causative roles in disease development by way of eicosanoids in the kidney.

“We will also determine how these metabolic disturbances in omega-3 fatty acid and eicosanoid metabolism are involved in mediating the effectiveness of treatment with fish oil,” Zivkovic said.

The scientists will measure the comprehensive blood lipid and eicosanoid profiles of IgAN patients and compare them with healthy individuals. Both groups will be measured before and after supplementation with fish oil. 

“We aim to find new biomarkers that will be used to assess metabolic status in patients with IgAN,” Zivkovic explained. “With these new biomarkers it will be possible to detect responsiveness to fish oil and monitor treatment progress. By comparing the changes in omega-3 fatty acids and eicosanoids that are associated with IgAN and fish oil treatment, we will also begin to unravel the causes of this disease and how omega-3 fatty acids play a role in its reversal.”

Said Hammock: "This is a unique opportunity for collaboration, using state-of-the-art new mass spectrometry equipment in our lab to probe the mechanism of action of common food supplements."

Hammock maintains an active research program in insect developmental biology and innovative methods of insect pest control. Due to his interest on the effects of pesticides on the environment and on human health, he developed broad interests in the human cardiovascular and inflammatory systems and how nutritional status and exposure to environmental chemicals may influence health. 

“At a fundamental level,” Hammock said, “the basic biology of insects is not so different from that of man.” 

Hammock has long collaborated with German, a biochemist noted for his work in using an analytical technique known as metabolomics to move toward individualizing medicine. Cell biologist Weiss pursues a variety of interests, including hardening of the arteries, restenosis and renal disease.

"UC Davis is unique in allowing me to draw on the skills in nutrition and food science of Angela Zivkovic and Bruce German on one hand, and the mass spectrometry laboratory run by Bruce Hammock on the other, to address fundamental science of immediate clinical interest," Weiss said.

Zivkovic, who received her doctorate in nutritional biology from UC Davis, researches the development of tools for metabolic health assessment. Her ultimate research goal is to pave the way to personalized nutrition approaches that can improve health and prevent disease in individuals.

"Recently available mass spectrometry equipment at UC Davis opens the door to personalized medicine," she said.