Home >> Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry, Volume 9, Number 1

Targeting the Fatty Acid Transport Proteins (FATP) to Understand the Mechanisms Linking Fatty Acid Transport to Metabolism

Authors: Black, Paul N.; Sandoval, Angel; Arias-Barrau, Elsa; DiRusso, Concetta C.

Source: Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry, Volume 9, Number 1, March 2009 , pp. 11-17(7)

Publisher: Bentham Science Publishers

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Abstract:

One principal process driving fatty acid transport is vectorial acylation, where fatty acids traverse the membrane concomitant with activation to CoA thioesters. Current evidence is consistent with the proposal that specific fatty acid transport (FATP) isoforms alone or in concert with specific long chain acyl CoA synthetase (Acsl) isoforms function to drive this energy-dependent process. Understanding the details of vectorial acylation is of particular importance as disturbances in lipid metabolism many times lead to elevated levels of circulating free fatty acids, which in turn increases fatty acid internalization and ectopic accumulation of triglycerides. This is associated with changes in fatty acid oxidation rates, accumulation of reactive oxygen species, the synthesis of ceramide and ER stress. The correlation between chronically elevated plasma free fatty acids and triglycerides with the development of obesity, insulin resistance and cardiovascular disease has led to the hypothesis that decreases in pancreatic insulin production, cardiac failure, arrhythmias, and hypertrophy are due to aberrant accumulation of lipids in these tissues. To this end, a detailed understanding of how fatty acids traverse the plasma membrane, become activated and trafficked into downstream metabolic pools and the precise roles provided by the different FATP and Acsl isoforms are especially important questions. We review our current understanding of vectorial acylation and the contributions by specific FATP and Acsl isoforms and the identification of small molecule inhibitors from high throughput screens that inhibit this process and thus provide new insights into the underlying mechanistic basis of this process.

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  • Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in the medicinal chemistry and rational drug design for the discovery of new Immunology, Endocrine & Metabolic Agents. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Immunology, Endocrine & Metabolic medicinal chemistry.

    Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in Immunology, Endocrine & Metabolic drug discovery.
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