Thermogenic flux induced by lignoceric acid in peroxisomes isolated from HepG2 cells and from X- adrenoleukodystrophy and control fibroblasts
Articolo
Data di Pubblicazione:
2019
Citazione:
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]
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Beta-oxidation; X-linked adrenoleukodystrophy; heat; isothermal calorimetry; peroxisomal disorders; very long-chain fatty acid (VLCFA)
Elenco autori:
A. Petroni, R. Paroni, A.M. Aloisi, M. Blasevich, N. Haman, D. Fessas
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