title: Increasing skeletal muscle fatty acid transport protein 1 (FATP1) targets fatty acids to oxidation and does not predispose mice to diet-induced insulin resistance.
abstract: OBJECTIVE
  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 < 0.05) palmitate transport (24%) and oxidation (35%), without altering triacylglycerol esterification or the intrinsic rate of palmitate oxidation in isolated mitochondria. In Mck/Fatp1 animals, Fatp1 mRNA and 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid uptake in skeletal muscle were upregulated (75%). However, insulin sensitivity and intramuscular triacylglycerol content did not differ between wild-type and Mck/Fatp1 mice following a 16 week high-fat diet. In insulin-resistant obese Zucker rats, LCFA transport and triacylglycerol accumulation were increased (85% and 24%, respectively), but this was not attributable to Fatp1 expression, as neither total cellular nor sarcolemmal FATP1 content were altered.
  
  
  CONCLUSIONS
  Overexpression of Fatp1 in skeletal muscle increased the rate of LCFA transport and channelled these lipids to oxidation, not to intramuscular lipid accumulation. Therefore, skeletal muscle FATP1 overabundance does not predispose animals to diet-induced insulin resistance.
authors: Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Rd, ANNU Building #70, Guelph, ON, Canada. ghollowa@uoguelph.ca
authors: G P
authors: GP
authors: Holloway
authors: C J
authors: CJ
authors: Chou
authors: J
authors: J
authors: Lally
authors: T
authors: T
authors: Stellingwerff
authors: A C
authors: AC
authors: Maher
authors: O
authors: O
authors: Gavrilova
authors: M
authors: M
authors: Haluzik
authors: H
authors: H
authors: Alkhateeb
authors: M L
authors: ML
authors: Reitman
authors: A
authors: A
authors: Bonen
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D050612:Fatty Acid Transport Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D010168:Palmitates; C493569:Slc27a1 protein, mouse; D014280:Triglycerides