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Diminished retinal complex lipid synthesis and impaired fatty acid β-oxidation associated with human diabetic retinopathy
- Source :
- JCI Insight
- Publication Year :
- 2021
- Publisher :
- American Society for Clinical Investigation, 2021.
-
Abstract
- BACKGROUND This study systematically investigated circulating and retinal tissue lipid determinants of human diabetic retinopathy (DR) to identify underlying lipid alterations associated with severity of DR. METHODS Retinal tissues were retrieved from postmortem human eyes, including 19 individuals without diabetes, 20 with diabetes but without DR, and 20 with diabetes and DR, for lipidomic study. In a parallel study, serum samples from 28 American Indians with type 2 diabetes from the Gila River Indian Community, including 12 without DR, 7 with mild nonproliferative DR (NPDR), and 9 with moderate NPDR, were selected. A mass-spectrometry–based lipidomic platform was used to measure serum and tissue lipids. RESULTS In the postmortem retinas, we found a graded decrease of long-chain acylcarnitines and longer-chain fatty acid ester of hydroxyl fatty acids, diacylglycerols, triacylglycerols, phosphatidylcholines, and ceramide(NS) in central retina from individuals with no diabetes to those with diabetes with DR. The American Indians’ sera also exhibited a graded decrease in circulating long-chain acylcarnitines and a graded increase in the intermediate-length saturated and monounsaturated triacylglycerols from no DR to moderate NPDR. CONCLUSION These findings suggest diminished synthesis of complex lipids and impaired mitochondrial β-oxidation of fatty acids in retinal DR, with parallel changes in circulating lipids. TRIAL REGISTRATION ClinicalTrials.gov NCT00340678. FUNDING This work was supported by NIH grants R24 DK082841, K08DK106523, R03DK121941, P30DK089503, P30DK081943, P30DK020572, P30 EY007003; The Thomas Beatson Foundation; and JDRF Center for Excellence (5-COE-2019-861-S-B).
- Subjects :
- Adult
Male
medicine.medical_specialty
Type 2 diabetes
Ceramides
Mass Spectrometry
Retina
White People
Diglycerides
chemistry.chemical_compound
Carnitine
Diabetes mellitus
Internal medicine
medicine
Humans
Retinopathy
Beta oxidation
Triglycerides
American Indian or Alaska Native
Aged
chemistry.chemical_classification
Diabetic Retinopathy
business.industry
Diabetes
Arizona
Fatty acid
Esters
Lipid metabolism
Retinal
Hispanic or Latino
General Medicine
Diabetic retinopathy
Middle Aged
medicine.disease
Mitochondria
Black or African American
Ophthalmology
Endocrinology
Diabetes Mellitus, Type 2
chemistry
Fatty acid oxidation
Case-Control Studies
Lipidomics
Disease Progression
Phosphatidylcholines
Female
Clinical Medicine
business
Subjects
Details
- ISSN :
- 23793708
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- JCI Insight
- Accession number :
- edsair.doi.dedup.....3aa86bb827888e46897f2d9b8b3085ee