This work analyzes the thermogenic flux induced by the very long-chain fatty acid (VLCFA) lignoceric acid (C24:0) in isolated peroxisomes. Specific metabolic alterations of peroxisomes are related to a variety of disorders, the most frequent one being the neurodegenerative inherited disease X-linked adrenoleukodystrophy (X-ALD). A peroxisomal transport protein is mutated in this disorder. Due to reduced catabolism and enhanced fatty acid elongation, VLCFA accumulate in plasma and in all tissues, contributing to the clinical manifestations of this disorder. During peroxisomal metabolism, heat is produced but it is considered lost. Instead, it is a form of energy that could play a role in molecular mechanisms of this pathology and other neurodegenerative disorders. The thermogenic flux induced by lignoceric acid (C24:0) was estimated by isothermal titration calorimetry in peroxisomes isolated from HepG2 cells and from fibroblasts obtained from X-linked adrenoleukodystrophy patients and healthy subjects. Heat flux induced by lignoceric acid in HepG2 peroxisomes was exothermic, indicating normal peroxisomal metabolism. In X-ALD peroxisomes the heat flux was endothermic, indicating the requirement of heat/energy, possibly for cellular metabolism. In fibroblasts from healthy subjects the effect was less pronounced than in HepG2, a kind of cell known to have greater FA metabolism than fibroblasts. Our hypothesis is that heat is not lost but it could act a s an activator, for example on the heat-sensitive pathway related to TRVP2 receptors. To investigate this hypothesis we focused on peroxisomal metabolism, considering that impaired heat generation could contribute to the development of peroxisomal neurodegenerative disorders.

Thermogenic flux induced by lignoceric acid in peroxisomes isolated from HepG2 cells and from X- adrenoleukodystrophy and control fibroblasts / A. Petroni, R. Paroni, A.M. Aloisi, M. Blasevich, N. Haman, D. Fessas. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - (2019). [Epub ahead of print]

Thermogenic flux induced by lignoceric acid in peroxisomes isolated from HepG2 cells and from X- adrenoleukodystrophy and control fibroblasts

A. Petroni
Primo
Project Administration
;
R. Paroni
Secondo
Writing – Review & Editing
;
M. Blasevich
Methodology
;
N. Haman
Penultimo
Methodology
;
D. Fessas
Ultimo
Supervision
2019

Abstract

This work analyzes the thermogenic flux induced by the very long-chain fatty acid (VLCFA) lignoceric acid (C24:0) in isolated peroxisomes. Specific metabolic alterations of peroxisomes are related to a variety of disorders, the most frequent one being the neurodegenerative inherited disease X-linked adrenoleukodystrophy (X-ALD). A peroxisomal transport protein is mutated in this disorder. Due to reduced catabolism and enhanced fatty acid elongation, VLCFA accumulate in plasma and in all tissues, contributing to the clinical manifestations of this disorder. During peroxisomal metabolism, heat is produced but it is considered lost. Instead, it is a form of energy that could play a role in molecular mechanisms of this pathology and other neurodegenerative disorders. The thermogenic flux induced by lignoceric acid (C24:0) was estimated by isothermal titration calorimetry in peroxisomes isolated from HepG2 cells and from fibroblasts obtained from X-linked adrenoleukodystrophy patients and healthy subjects. Heat flux induced by lignoceric acid in HepG2 peroxisomes was exothermic, indicating normal peroxisomal metabolism. In X-ALD peroxisomes the heat flux was endothermic, indicating the requirement of heat/energy, possibly for cellular metabolism. In fibroblasts from healthy subjects the effect was less pronounced than in HepG2, a kind of cell known to have greater FA metabolism than fibroblasts. Our hypothesis is that heat is not lost but it could act a s an activator, for example on the heat-sensitive pathway related to TRVP2 receptors. To investigate this hypothesis we focused on peroxisomal metabolism, considering that impaired heat generation could contribute to the development of peroxisomal neurodegenerative disorders.
Beta-oxidation; X-linked adrenoleukodystrophy; heat; isothermal calorimetry; peroxisomal disorders; very long-chain fatty acid (VLCFA)
Settore CHIM/02 - Chimica Fisica
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore BIO/14 - Farmacologia
2019
1-apr-2019
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/632043
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