Tissue acylcarnitine status in a mouse model of mitochondrial β-oxidation deficiency during metabolic decompensation due to influenza virus infection

Abstract

Despite judicious monitoring and care, patients with fatty acid oxidation disorders may experience metabolic decompensation due to infection which may result in rhabdomyolysis, cardiomyopathy, hypoglycemia and liver dysfunction and failure. Since clinical studies on metabolic decompensation are dangerous, we employed a preclinical model of metabolic decompensation due to infection. By infecting mice with mouse adapted influenza and using a pair-feeding strategy in a mouse model of long-chain fatty acid oxidation (Acadvl), our goals were to isolate the effects of infection on tissue acylcarnitines and determine how they relate to their plasma counterparts. Applying statistical data reduction techniques (Partial Least Squares-Discriminant Analysis), we were able to identify critical acylcarnitines that were driving differentiation of our experimental groups for all the tissues studied. While plasma displayed increases in metabolites directly related to mouse VLCAD deficiency (e.g. C16 and C18), organs like the heart, muscle and liver also showed involvement of alternative pathways (e.g. medium-chain FAO and ketogenesis), suggesting adaptive measures. Matched correlation analyses showed strong correlations (r > 0.7) between plasma and tissue levels for a small number of metabolites. Overall, our results demonstrate that infection as a stress produces perturbations in metabolism in Acadvl that differ greatly from WT infected and Acadvl pair-fed controls. This model system will be useful for studying the effects of infection on tissue metabolism as well as evaluating interventions aimed at modulating the effects of metabolic decompensation.

The Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Impairment and the Brain Lipidome in a Cuprizone-Induced Mouse Model of Demyelination

“…However, the reductions of MG in both PFC and striatum were not normalized by rTMS, suggesting that the glycerolipids in the PFC and striatum are more vulnerable than hippocampus to CPZ. AcCa compounds in the brain functionally alter and stabilize membranes, improving mitochondrial function and increasing antioxidant activity ( Rutkowsky et al, 2014 ; Tarasenko et al, 2018 ). The present study also found that CPZ treatment decreased the levels of AcCa only in the PFC, which was normalized by rTMS, suggesting that the AcCa in the PFC are more vulnerable than other brain region and might be associated to the therapeutic effects of rTMS.…”

The methanolic extract of Garcinia atroviridis (MeGa) reduces body weight and food intake, and improves lipid profiles by altering the lipid metabolism: a rat model

“…Acylcarnitine is the main transporter involved in the energy production process. It carries activated longchain fatty acids (the breakdown products of fatty acids and amino acids) into mitochondria for the β-oxidation process (Tarasenko et al, 2018). Acylcarnitine also serves as an important biomarker of mitochondrial dysfunction with an increase of acylcarnitines (Chen et al, 2015).…”

Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma

“…The main function of acylcarnitines is involved in long-chain fatty acids (LCFAs) β-oxidation ( Figure 2 ). They serve as carriers to transport activated LCFAs into mitochondria for subsequent β-oxidation to provide energy for cell activities [ 29 ]. The enzymes that regulate these processes are mainly long-chain acyl-coenzyme A synthetase (LACS), carnitine/acylcarnitine translocase (CACT), carnitine palmitoyl-transferase 1 and 2 (CPT1 and CPT2) [ 30 ].…”