Fatty acid binding proteins (FABP) are a group of intracellular proteins that act to regulate the lipid balance of the cell. They are important to understand because they may play a role in inflammation and metabolic disturbances that may be associated with insulin resistance, metabolic syndrome and obesity. It is known that individuals with insulin resistance have raised levels of circulating fatty acids, possibly caused by de novo lipogenesis in the liver as a result of fructose ingestion (here). This raised level of serum fatty acids is though to cause inflammation and insulin resistance and subsequently lead to diabetes and obesity by the modification of glucose metabolism within cells. The FABP that reside in the cells may modulate this insulin resistance and inflammatory reaction to lipids because they distribute extracellular fatty acids and lipids to their intracellular targets.
The FABP are present in the cytoplasm of cells where they are integral to the cells lipid signalling cascades. The role of FABP is to bind long chain saturated and unsaturated fatty acids (e.g. palmitic acid or oleic acid), eicosanoids (e.g. prostaglandins or leukotrienes) and other lipid molecules (e.g. cholesterol). The FABP may also import, transport, store and export fatty acids. Fatty acids are liberated from circulating lipoproteins by the action of lipases on the cell membrane, and then delivered into the cell via transporters such as fatty acid tranlocase/CD36 and fatty acid transport protein. Fatty acid binding protein may then link these fatty acids to the designated targets such as c-Jun N-terminal kinase (JNK) or the nuclear hormone receptor PPARγ, which then elicits a particular cellular response. The FABP may also modify hormone sensitive lipase activity.
Obesity can be thought of as a disease of chronic inflammation, as evidenced by the inflammatory cytokines secreted from adipose tissue in obese subjects. This is because adipocytes and macrophages share common metabolic signalling pathways. It is likely that FABP regulate lipid balance in a similar way in both macrophages and adipocytes which in turn respond with the same inflammatory and metabolic processes. With respect to the effects of fatty acids on insulin resistance, FABP can interact with JNK, which in turn appears able to interfere with the action of insulin on the insulin receptor (insulin receptor substrate-1; IRS-1). This suggests a role for FABP and the activation of JNK in the development of insulin resistance. The chronic inflammation and insulin resistance associated with poor diet may therefore result in a profile of fatty acids binding to the FABP which ultimately leads to chronic degenerative disease.
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