» Articles » PMID: 30031688

Tissue Acylcarnitine Status in a Mouse Model of Mitochondrial β-oxidation Deficiency During Metabolic Decompensation Due to Influenza Virus Infection

Overview
Journal Mol Genet Metab
Specialty Endocrinology
Date 2018 Jul 23
PMID 30031688
Citations 29
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Multiomics approach identifies dysregulated lipidomic and proteomic networks in Parkinson's disease patients mutated in TMEM175.

Carrillo F, Ghirimoldi M, Fortunato G, Palomba N, Ianiro L, De Giorgis V NPJ Parkinsons Dis. 2025; 11(1):23.

PMID: 39856101 PMC: 11760379. DOI: 10.1038/s41531-024-00853-5.


Altered Metabolites in Hepatocellular Carcinoma (HCC) Paving the Road for Metabolomics Signature and Biomarkers for Early Diagnosis of HCC.

Al-Amodi H, Kamel H Cureus. 2024; 16(10):e71968.

PMID: 39569240 PMC: 11576499. DOI: 10.7759/cureus.71968.


Human inborn errors of long-chain fatty acid oxidation show impaired inflammatory responses to TLR4-ligand LPS.

Mosegaard S, Twayana K, Denis S, Kroon J, Schomakers B, van Weeghel M FASEB Bioadv. 2024; 6(9):337-350.

PMID: 39399475 PMC: 11467727. DOI: 10.1096/fba.2024-00060.


Deciphering metabolomics and lipidomics landscape in zebrafish hypertrophic cardiomyopathy model.

Jacob S, Abuarja T, Shaath R, Hasan W, Balayya S, Abdelrahman D Sci Rep. 2024; 14(1):21902.

PMID: 39300306 PMC: 11413214. DOI: 10.1038/s41598-024-72863-5.


Eight-year diet and physical activity intervention affects serum metabolites during childhood and adolescence: A nonrandomized controlled trial.

Zarei I, Eloranta A, Klavus A, Vaisto J, Lehtonen M, Mikkonen S iScience. 2024; 27(7):110295.

PMID: 39055945 PMC: 11269805. DOI: 10.1016/j.isci.2024.110295.


References
1.
Exil V, Roberts R, Sims H, McLaughlin J, Malkin R, Gardner C . Very-long-chain acyl-coenzyme a dehydrogenase deficiency in mice. Circ Res. 2003; 93(5):448-55. DOI: 10.1161/01.RES.0000088786.19197.E4. View

2.
Cox K, Hamm D, Millington D, Matern D, Vockley J, Rinaldo P . Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse. Hum Mol Genet. 2001; 10(19):2069-77. DOI: 10.1093/hmg/10.19.2069. View

3.
Likos A, Kelvin D, Cameron C, Rowe T, Kuehnert M, Norris P . Influenza viremia and the potential for blood-borne transmission. Transfusion. 2007; 47(6):1080-8. DOI: 10.1111/j.1537-2995.2007.01264.x. View

4.
Taroni F, Uziel G . Fatty acid mitochondrial beta-oxidation and hypoglycaemia in children. Curr Opin Neurol. 1996; 9(6):477-85. DOI: 10.1097/00019052-199612000-00015. View

5.
BRATOVANOV D . [A new method of determining and analyzing seasonality of acute infectious diseases]. Zh Mikrobiol Epidemiol Immunobiol. 1970; 47(9):62-7. View