Lipid Dynamics in a Mouse Model of Cardiac-Specific Overexpression of the Fatty Acid Transporter, FATP1
thesisposted on 01.07.2016 by Ellen Shamansky
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The uptake and level of long-chain fatty acids in the myocardium of human subjects are not influenced by estrogen, although estrogen has been shown to correlate with higher rates of myocardial fatty acid oxidation in women (Herrero et al. 2005). This contributed to the hypothesis that fatty acid uptake and intracellular lipid handling occur differently in male and female mice with cardiac-specific overexpression of the fatty acid transport protein, FATP1. Rates of long-chain fatty acid uptake, esterification, and turnover from the triglyceride pool were examined in the hearts of male and female mice with cardiac-specific overexpression of FATP1 to identify potential points of sexual dimorphism in intramyocardial lipid handling. Dynamic 13C NMR experiments and liquid chromatography/mass spectrometry were used to quantify the time constant for long-chain fatty acid uptake, the level of 13C enrichment in the triglyceride pool, and triglyceride turnover. Results showed a trend towards faster uptake, greater triglyceride enrichment, and higher triglyceride turnover in FATP1 males compared to non-transgenic males. In females, there was a trend towards equal uptake and triglyceride enrichment, but FATP1 females displayed faster triglyceride turnover relative to non-transgenic females. Further investigation is needed to confirm these findings and determine if FATP1 mediates a sex-dependent mechanism that results in altered lipid metabolism.