Proteomic profiling of fatty acid binding proteins in muscular dystrophy

ABSTRACT

Introduction: Duchenne muscular dystrophy is a neuromuscular disorder, which is caused by abnormalities in the DMD gene that encodes the membrane cytoskeletal protein dystrophin. Besides progressive skeletal muscle wasting, dystrophinopathy also affects non-skeletal muscle tissues, including cells in the cardio-respiratory system, the central nervous system, the liver and the kidney.

Areas covered: This review summarizes the proteomic characterization of a key class of lipid chaperones, the large family of fatty acid binding proteins, and their potential role in muscular dystrophy. Recent proteomic surveys using animal models and patient specimens are reviewed. Pathobiochemical changes in specific proteoforms of fatty acid binding protein in the multi-system pathology of dystrophinopathy are discussed.

Expert opinion: The mass spectrometric identification of distinct changes in fatty acid binding proteins in muscle, heart, liver, kidney and serum demonstrates that considerable alterations occur in key steps of metabolite transport and fat metabolism in muscular dystrophy. These new findings might be helpful to further develop a comprehensive biomarker signature of metabolic changes in X-linked muscular dystrophy, which should improve (i) our understanding of complex pathobiochemical changes due to dystrophin deficiency, (ii) the identification of novel therapeutic targets, and (iii) the design of differential diagnostic, prognostic and therapy-monitoring approaches.

KEYWORDS:

• Duchenne muscular dystrophy
• dystrophinopathy
• FABP1
• FABP3
• FABP5
• fatty acid binding protein
• fat metabolism
• H-FABP
• lipid chaperone
• serum

Article Highlights

• Fatty acid binding proteins are crucial lipid chaperones involved in the intra- and extracellular transportation of hydrophobic metabolites

• Various FABP isoforms play important roles in energy metabolism and cellular signalling mechanisms

• Mass spectrometry-based proteomics has been instrumental in the identification of muscle-associated FABP proteoforms.

• Skeletal muscles contain FABP3 (H-FABP), as well as differing amounts of the isoforms FABP1, FABP2, FABP4 and FABP5.

• Duchenne muscular dystrophy exhibits changed FABP expression levels and abnormal fat metabolism.

• FABP3 is decreased in dystrophic skeletal and cardiac muscles, but elevated in serum from Duchenne patients

• Dystrophin deficiency was shown to be associated with elevated levels of FABP5 in the liver and FABP1 in the kidney

• FABP expression changes may be exploitable for the refinement of the biomarker signature of dystrophinopathy

• Serum FABP3 might be useful as a new type of minimally invasive biomarker of muscular dystrophy

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was supported by the Kathleen Lonsdale Institute for Human Health Research at Maynooth University.