Transgenic fatty acid transport one (FATP1) non-human knockout mammals uses thereof

A method for identifying an agent that inhibits an FATP1 activity comprising:

• a) optionally inducing insulin resistance in a non-human mammal comprising a wild-type FATP1 gene and a non-human mammal comprising a disrupted FATP1 gene, or providing an insulin-resistant non-human mammal comprising a wild-type FATP1 gene and a non-human mammal comprising a disrupted FATP1 gene;
• b. administering an agent to the mammal comprising a wild-type FATP1 gene;
• c. administering an agent to the mammal comprising a disrupted FATP1 gene;
• d. determining a biological activity level of the mammals;
• and
• e. comparing the biological activity of the mammal whose genome comprises a wild-type FATP1 gene and the mammal whose genome comprises a disrupted FATP1 gene,
• wherein the biological activity measured is selected from the group consisting of glucose uptake, glucose clearance, muscle triglyceride accumulation, fatty acid transport, and FATP1 mediated acyl-CoA synthetase activity;
• and
• whereby if the biological activity of the mammal whose genome comprises a wild-type FATP1 gene is similar to the biological activity of the mammal whose genome comprises a disrupted FATP1 gene, then the agent inhibits FATP1.

A method for identifying a candidate agent useful for the treatment of an FATP1-mediated metabolic disorder comprising:

• a) contacting a test agent with a composition comprising mammalian FATP1;
• b) measuring the activity of FATP1 the presence of the test agent;
• c) comparing the level of FATP1 activity in the presence of the test agent to the level of FATP1 activity in the absence of the test agent;
• and
• d) identifying the agent as a candidate agent useful for the treatment of an FATP1 mediated metabolic disorder where the level of the FATP1 activity is altered in the presence of the test agent;
• wherein the FATP1 activity measured is selected from the group consisting of acyl-CoA synthetase enzyme activity, fatty acid transport, and glucose uptake;
• and
• wherein the FATP1-mediated disorder is selected from the group consisting of insulin resistance, non-insulin dependent diabetes mellitus, and cellular triglyceride accumulation.