Decreased Fatty Acid β-Oxidation in Riboflavin-Responsive, Multiple Acylcoenzyme a Dehydrogenase-Deficient Patients Is Associated with an Increase in Uncoupling Protein-3

Aaron P. Russell, Patrick Schrauwen, Emmanuel Somm, Giacomo Gastaldi, Matthijs K C Hesselink, Gert Schaart, Esther Kornips, Sing Kai Lo, Daniela Bufano, Jean Paul Giacobino, Patrick Muzzin, Mara Ceccon, Corrado Angelini, Lodovica Vergani

Research output: Contribution to journalArticlepeer-review

Abstract

Riboflavin-responsive, multiple acylcoenzyme A dehydrogenase deficiency (RR-MAD), a lipid storage myopathy, is characterized by, among others, a decrease in fatty acid (FA) β-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 β-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 β-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 β-oxidation.

Original languageEnglish
Pages (from-to)5921-5926
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number12
DOIs
Publication statusPublished - Dec 2003

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Fingerprint

Dive into the research topics of 'Decreased Fatty Acid β-Oxidation in Riboflavin-Responsive, Multiple Acylcoenzyme a Dehydrogenase-Deficient Patients Is Associated with an Increase in Uncoupling Protein-3'. Together they form a unique fingerprint.

Cite this