Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets

Fatty acid-binding proteins (FABPs) are members of a highly conserved family of proteins central to lipid-mediated processes and related metabolic and immune response pathways. Here, the authors review the functions of individual FABP family members, emphasizing the potential of FABP inhibition as a novel strategy in the treatment of disorders of the metabolic syndrome including obesity, diabetes and atherosclerosis. Lipids are vital components of many biological processes and crucial in the pathogenesis of numerous common diseases, but the specific mechanisms coupling intracellular lipids to biological targets and signalling pathways are not well understood. This is particularly the case for cells burdened with high lipid storage, trafficking and signalling capacity such as adipocytes and macrophages. Here, we discuss the central role of lipid chaperones — the fatty acid-binding proteins (FABPs) — in lipid-mediated biological processes and systemic metabolic homeostasis through the regulation of diverse lipid signals, and highlight their therapeutic significance. Pharmacological agents that modify FABP function may provide tissue-specific or cell-type-specific control of lipid signalling pathways, inflammatory responses and metabolic regulation, potentially providing a new class of drugs for diseases such as obesity, diabetes and atherosclerosis.