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Decreased fatty acit Â-oxidation in riboflavin-responsive, multiple acylocoenzyme a dehydrogenase-deficient patients is associated with an increase in uncoupling protein-3

journal contribution
posted on 01.01.2003, 00:00 authored by Aaron RussellAaron Russell, P Schrauwen, E Somm, G Gastaldi, M Hesselink, G Schaart, E Kornips, Sing Lo, D Bufano, J P Giacobino, P Muzzin, M Ceccon, C Angelini, L Vergani
Riboflavin-responsive, multiple acylcoenzyme A dehydrogenase deficiency (RR-MAD), a lipid storage myopathy, is characterized by, among others, a decrease in fatty acid (FA) ß-oxidation capacity. Muscle uncoupling protein 3 (UCP3) is up-regulated under conditions that either increase the levels of circulating free FA and/or decrease FA ß-oxidation. Using a relatively large cohort of seven RR-MAD patients, we aimed to better characterize the metabolic disturbances of this disease and to explore the possibility that it might increase UCP3 expression. A battery of biochemical and molecular tests were performed, which demonstrated decreases in FA ß-oxidation and in the activities of respiratory chain complexes I and II. These metabolic alterations were associated with increases of 3.1- and 1.7-fold in UCP3 mRNA and protein expression, respectively. All parameters were restored to control values after riboflavin treatment. We postulate that the up-regulation of UCP3 in RR-MAD is due to the accumulation of muscle FA/acylCoA. RR-MAD is an optimal model to support the hypothesis that UCP3 is involved in the outward translocation of an excess of FA from the mitochondria and to show that, in humans, the effects of FA on UCP3 expression are direct and independent of fatty acid ß-oxidation.

History

Journal

Journal of clinical endocrinology and metabolism

Volume

88

Issue

12

Pagination

5921 - 5926

Publisher

The Endocrine Society

Location

Chevy Chase, MD

ISSN

0021-972X

eISSN

1945-7197

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2003 The Endocrine Society