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Fatty acid transport protein 6 (FATP6), also known as Solute carrier family 27 member 6 (SLC27A6), is a transmembrane protein predominantly expressed in the heart, specifically localized to the sarcolemma of cardiomyocytes [1, 6, 7]. It serves a dual role as a transporter of long-chain fatty acids (LCFAs) and an enzyme with acyl-CoA synthetase activity, facilitating both the cellular uptake and the metabolic activation of fatty acids, which are the primary energy source for the myocardium [1, 6, 8]. Dysregulation of FATP6 is implicated in the pathogenesis of various lipid-related cardiac disorders, including cardiomyopathy, heart failure, and hypertrophy, as well as systemic metabolic conditions such as obesity and metabolic syndrome [1, 3, 8]. Genetic variations in the SLC27A6 gene, such as the 7T>A polymorphism, have been associated with protective effects against cardiovascular disease and metabolic syndrome traits [1]. While no specific FDA-approved drugs currently target FATP6, it is recognized as a promising therapeutic target for managing cardiac lipotoxicity and metabolic dysfunction [2, 3, 8]. Current research focuses on identifying selective small-molecule inhibitors that can modulate fatty acid flux to treat metabolic diseases without compromising essential cardiac energy production [2, 22].
Inhibition of fatty acid uptake and acyl-CoA synthetase activity to modulate lipid flux and prevent ectopic lipid accumulation.
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