Abstract: SA-PO998
Plasma Lipidomic Analysis Reveals Differential Mitochondrial Fatty Acid Metabolism in Diabetic and Non-Diabetic CKD-Associated Heart Failure
Session Information
- Hypertension and CVD: Mechanisms - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Afshinnia, Farsad, University of Michigan, Ann Arbor, Michigan, United States
- Rajendiran, Thekkelnaycke, Univeraity of MIchigan, Ann Arbor, Michigan, United States
- Pennathur, Subramaniam, University of Michigan, Ann Arbor, Michigan, United States
Group or Team Name
- Michigan Kidney Translational Core CPROBE Investigator Group
Background
Cardiac myocytes utilize fatty acids predominantly for mitochondrial energy metabolism. Diabetic cardiomyopathy is characterized by increased β-oxidation due to elevated free fatty acids (FFA). Alterations in energy metabolism in diabetic and non-diabetic heart failure (HF) with chronic kidney disease (CKD) is less clear. This study investigated lipid metabolism by comparing the FFAs, acylcarnitines (ACs, a metric of β-oxidation), and complex lipids in diabetic and non-diabetic CKD patients with and without HF.
Methods
From the Clinical Phenotyping Resource and Biobank Core (CPROBE) 214 patients at various stages of CKD were selected for plasma lipidomic analysis. Of the 89 patients with diabetes, 10 had HF; in 125 subjects without diabetes 21 had HF. Plasma lipids and ACs were measured using mass spectrometry based untargeted and targeted lipidomic platforms, respectively.
Results
The mean age was 60 years (standard deviation=16). One hundred ten patients were males (51.4%), 64 were African-Americans (29.9%), and 150 were Caucasians (70.1%). In patients without diabetes median (interquartile range) of ACs in patients with HF were significantly higher than the patients without HF (Table, P<0.05 for all). In patients with diabetes the ACs were not different in patients with and without HF. Mixed linear model showed decreased abundance of saturated FFAs with lower carbon numbers in non-diabetic patients with HF, but an increased abundance of these metabolites in diabetic patients with HF as compared to no HF (p=0.002). In non-diabetic patients with HF, linear regression showed an inverse association between abundance of saturated FFAs with intermediate-chain ACs (p=0.025) and a direct association with long-chain ACs (p=0.044), a relationship which disappeared in diabetic patients with HF.
Conclusion
In non-diabetic HF, increased ACs at the cost of depletion of saturated FFAs is noted, while in diabetic HF saturated FFA increases without change in AC. Differential energy metabolism in HF with and without diabetes in CKD highlights the need for differential targeted therapies by etiology to optimize heart function and outcome in CKD.
Table 1
Funding
- NIDDK Support