The adipocyte fatty acid transport proteins (FATPs), FATP1 and FATP4, have been
implicated in both lipid influx and storage and understanding their role in adipose tissue
would gain insight into the persistence of metabolic disorders, such as type 2 diabetes.
FATP1 was previously determined to be an acyl-CoA synthetase and work described in
this thesis additionally explored the acyl-CoA synthetase activity of purified FATP4.
FATP4 was found to be a more robust acyl-CoA synthetase than FATP1. Through the
use of RNAi in cultured adipocytes, silencing the expression of either FATP1 or FATP4
results in cellular phenotype demonstrating improved insulin responsiveness.
Interestingly, silencing FATP1 abolished insulin-stimulated long-chain fatty acid
(LCFA) influx, whereas silencing FATP4 had no effect on LCFA influx despite its
higher activity. Furthermore, the expression of FATP1 was demonstrated to be
important for the activation of the AMP-activated protein kinase during insulinstimulated
LCFA influx. In addition to the cytoplasmic localization of FATP1, it was
also found to exhibit mitochondrial localization. Further analysis demonstrated a novel
role in the regulation of TCA cycle function and mitochondrial energy metabolism, in
part, through the interaction of FATP1 with the 2-oxoglutarate dehydrogenase complex,
a rate-limiting step in the TCA cycle. This work shines light on how FATPs may play
broader roles in metabolism that previously appreciated and the potential implications
associated with such roles.
University of Minnesota Ph.D. dissertation. July 2009. Major: Biochemistry, Molecular Biology, and Biophysics. Advisor: David A. Bernlohr. 1 computer file (PDF) ix, 170 pages.
Wiczer, Brian Michael.
Biochemical and functional characterization of fatty acid transport proteins..
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