PT - JOURNAL ARTICLE AU - Wu, Qiwei AU - Kazantzis, Melissa AU - Doege, Holger AU - Ortegon, Angelica M. AU - Tsang, Bernice AU - Falcon, Alaric AU - Stahl, Andreas TI - Fatty Acid Transport Protein 1 Is Required for Nonshivering Thermogenesis in Brown Adipose Tissue AID - 10.2337/db06-0749 DP - 2006 Dec 01 TA - Diabetes PG - 3229--3237 VI - 55 IP - 12 4099 - http://diabetes.diabetesjournals.org/content/55/12/3229.short 4100 - http://diabetes.diabetesjournals.org/content/55/12/3229.full SO - Diabetes2006 Dec 01; 55 AB - Nonshivering thermogenesis in brown adipose tissue (BAT) generates heat through the uncoupling of mitochondrial β-oxidation from ATP production. The principal energy source for this process is fatty acids that are either synthesized de novo in BAT or are imported from circulation. How uptake of fatty acids is mediated and regulated has remained unclear. Here, we show that fatty acid transport protein (FATP)1 is expressed on the plasma membrane of BAT and is upregulated in response to cold stimuli, concomitant with an increase in the rate of fatty acid uptake. In FATP1-null animals, basal fatty acid uptake is reduced and remains unchanged following cold exposure. As a consequence, FATP1 knockout (KO) animals display smaller lipid droplets in BAT and fail to defend their core body temperature at 4°C, despite elevated serum free fatty acid levels. Similarly, FATP1 is expressed by the BAT-derived cell line HIB-1B upon differentiation, and both fatty acid uptake and FATP1 protein levels are rapidly elevated following isoproterenol stimulation. Stimulation of fatty uptake by isoproterenol required both protein kinase A and mitogen-activated kinase signaling and is completely dependent on FATP1 expression, as small-hairpin RNA–mediated knock down of FATP1 abrogated the effect.