Oxylipin profiling of alzheimer's disease in nondiabetic and type 2 diabetic elderly

Authors: MORRIS, JILL - University Of Kansas; PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC); JOHN, CASEY - University Of Kansas; GREEN, ZACHARY - University Of Kansas; THYFAULT, JOHN - University Of Kansas; Ferruzzi, Mario

Submitted to: Metabolites
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/3/2019
Publication Date: 9/5/2019
Citation: Morris, J.K., Piccolo, B.D., John, C.S., Green, Z.D., Thyfault, J.P., Adams, S.H. 2019. Oxylipin profiling of alzheimer's disease in nondiabetic and type 2 diabetic elderly. Metabolites. 9(9): 177. https://doi.org/10.3390/metabo9090177.
DOI: https://doi.org/10.3390/metabo9090177

Interpretive Summary: Oxygenated lipids, called "oxylipins," serve a variety of important signaling roles in the body, but all the functions of these molecules are not understood. Oxylipins have been linked to inflammation and vascular function, and blood patterns have been shown to differ in type 2 diabetes (T2D). Because these factors (inflammation, vascular function, diabetes) are also associated with Alzheimer's disease (AD) risk, we set out to characterize the serum oxylipin profile in elderly and AD subjects to understand if there are shared patterns between AD and T2D. Using these unique comparisons, a better understanding of which blood fats associate with diabetes and brain health could be determined. This enables the possibility to test these specific fats across the lifespan to see if patterns relate to T2D risk and brain function. We obtained serum from 126 well-characterized, overnight-fasted elderly individuals who underwent a stringent cognitive evaluation and were determined to be cognitively healthy or AD. Because the oxylipin profile may also be influenced by T2D, nondiabetic and T2D participants were analyzed separately. Within nondiabetic individuals, cognitively healthy persons had higher levels of the nitrolipid 10-nitrooleate (16.8% higher) compared to AD participants. AD subjects had higher levels of all four DiHETrE metabolite species: 14,15-DiHETrE (18% higher), 11,12 DiHETrE (18% higher), 8,9-DiHETrE (23% higher), and 5,6-DiHETrE (15% higher). Within T2D participants, we observed elevations in 14,15-DiHETE (66% higher), 17,18-DiHETE (29% higher) and 17-HDoHE (105% higher) and summed fatty acid diols (85% higher) in subjects with AD compared to cognitively healthy elderly. The consistent effects on groups of molecules with similar physiological roles, as well as clear differences in the AD-related profiles within nondiabetic and T2D individuals, warrants further research into these molecules in the context of AD and brain health. In addition, these specific fatty acids may be evaluated across the lifespan to determine if their patterns in blood reflect differences in brain function and behavior, regardless of diabetes status.

Technical Abstract: Oxygenated lipids, called "oxylipins," serve a variety of important signaling roles within the cell. Oxylipins have been linked to inflammation and vascular function, and blood patterns have been shown to differ in type 2 diabetes (T2D). Because these factors (inflammation, vascular function, diabetes) are also associated with Alzheimer's Disease (AD) risk, we set out to characterize the serum oxylipin profile in elderly and AD subjects to understand if there are shared patterns between AD and T2D. We obtained serum from 126 well-characterized, overnight-fasted elderly individuals who underwent a stringent cognitive evaluation and were determined to be cognitively healthy or AD. Because the oxylipin profile may also be influenced by T2D, we assessed nondiabetic and T2D subjects separately. Within nondiabetic individuals, cognitively healthy subjects had higher levels of the nitrolipid 10-nitrooleate (16.8% higher) compared to AD subjects. AD subjects had higher levels of all four DiHETrE-species: 14,15-DiHETrE (18% higher), 11,12 DiHETrE (18% higher), 8,9-DiHETrE (23% higher), and 5,6-DiHETrE (15% higher). Within T2D participants, we observed elevations in 14,15-DiHETE (66% higher), 17,18-DiHETE (29% higher) and 17-HDoHE (105% higher) and summed fatty acid diols (85% higher) in subjects with AD compared to cognitively healthy elderly, with no differences in the DiHETrE species between groups. Although these effects were no longer significant following stringent adjustment for multiple comparisons, the consistent effects on groups of molecules with similar physiological roles, as well as clear differences in the AD-related profiles within nondiabetic and T2D individuals, warrants further research into these molecules in the context of AD.