Gimeno Ruth E
Department of Cardiovascular and Metabolic Diseases, Wyeth Research, Cambridge, Massachusetts 02140, USA.
Curr Opin Lipidol. 2007 Jun;18(3):271-6. doi: 10.1097/MOL.0b013e3281338558.
Fatty acid transport proteins are a family of proteins involved in fatty acid uptake and activation. This review summarizes recent progress in elucidating the function of fatty acid transport proteins.
Recent experiments clearly establish FATP1 as a regulated fatty acid transporter in both adipose tissue and muscle with important roles in energy homeostasis, thermogenesis and insulin resistance. Knockout of FATP5 in mice show it to be a bifunctional protein required for both hepatic fatty acid uptake and bile acid reconjugation. The most striking phenotype of FATP4 deletion is a defect in skin homeostasis, which may be due to its very long chain acyl-coenzyme A synthetase activity. Fatty acid transport proteins are increasingly being recognized as multifunctional proteins that can mediate the uptake of fatty acids as well as catalyze the formation of coenzyme A derivatives using long-chain and very-long chain fatty acids, bile acids and bile acid precursors as substrates.
Modulation of fatty acid transport protein function can result in altered energy homeostasis and insulin sensitivity, defective skin homeostasis, and altered bile acid metabolism. Both fatty acid uptake and enzymatic activity of fatty acid transport proteins likely contribute to these phenotypes. Future studies are needed to better understand the molecular mechanism of fatty acid transport protein function and the physiological role of FATP2, FATP3, and FATP6.
脂肪酸转运蛋白是一类参与脂肪酸摄取和活化的蛋白质。本综述总结了在阐明脂肪酸转运蛋白功能方面的最新进展。
最近的实验明确证实FATP1是脂肪组织和肌肉中一种受调控的脂肪酸转运蛋白,在能量稳态、产热和胰岛素抵抗中起重要作用。敲除小鼠体内的FATP5表明它是肝脏脂肪酸摄取和胆汁酸再结合所需的双功能蛋白。FATP4缺失最显著的表型是皮肤稳态缺陷,这可能归因于其超长链酰基辅酶A合成酶活性。脂肪酸转运蛋白越来越被认为是多功能蛋白,它既能介导脂肪酸的摄取,又能以长链和超长链脂肪酸、胆汁酸及胆汁酸前体为底物催化辅酶A衍生物的形成。
脂肪酸转运蛋白功能的调节可导致能量稳态和胰岛素敏感性改变、皮肤稳态缺陷以及胆汁酸代谢改变。脂肪酸转运蛋白的脂肪酸摄取和酶活性可能都对这些表型有影响。未来需要开展研究以更好地理解脂肪酸转运蛋白功能的分子机制以及FATP2、FATP3和FATP6的生理作用。