Increasing skeletal muscle fatty acid transport protein 1 (FATP1) targets fatty acids to oxidation and does not predispose mice to diet-induced insulin resistance

Aims/hypothesis We examined in skeletal muscle (1) whether fatty acid transport protein (FATP) 1 channels long-chain fatty acid (LCFA) to specific metabolic fates in rats; and (2) whether FATP1-mediated increases in LCFA uptake exacerbate the development of diet-induced insulin resistance in mice. We also examined whether FATP1 is altered in insulin-resistant obese Zucker rats. Methods LCFA uptake, oxidation and triacylglycerol esterification rates were measured in control and Fatp1 -transfected soleus muscles to determine FATP1-mediated lipid handling. The effects of FATP1 on insulin sensitivity and triacylglycerol accumulation were determined in high-fat diet-fed wild-type mice and in muscle-specific Fatp1 (also known as Slc27a1 ) overexpressing transgenic mice driven by the muscle creatine kinase ( Mck [also known as Ckm ]) promoter. We also examined the relationship between FATP1 and both fatty acid transport and metabolism in insulin-resistant obese Zucker rats. Results Transient Fatp1 overexpression in soleus muscle increased ( p