Project Details

Description

The objective of this research is to study the transfer of free
fatty acids (ffa) in the intestine at the molecular level, in order
to elucidate the mechanisms by which ffa assimilation occurs. The
ultimate aim of these studies is to learn how to control lipid
assimilation by regulation of rate limiting processes. The
proposed studies will address the gaps in our knowledge concerning
the regulation of ffa transfer, both within the intestinal lumen
and within the cytoplasm of the enterocyte. The approach used will
be an integrated one, combining the techniques of purified model
lipid systems with reconstituted systems of cell membranes and
cytoplasmic components. Recent work has shown that during the course of intestinal lipid
digestion, two product phase are formed, a micelle phase and a
unilamellar vesicle phase. The proposed studies will use a
fluorescence assay recently developed by the applicant to compare
the kinetics of ffa transfer from these two distinct lipid phases
to acceptor membranes, and to determine the molecular mechanisms
and rate limiting steps by which transfer from each of these phases
occurs. The majority of ffa within the enterocyte cytoplasm are bound to
fatty acid binding protein(s) (FABP). Our preliminary studies have
shown that when ffa are bound to FABP, the fatty acyl chain is
highly constrained within a hydrophobic pocket. The proposed
studies will continue to investigate the physical nature of the
FABP binding site of ffa, and will characterize and compare ffa
binding to FABP v. ffa binding to membranes, in order to assess the
relative roles of these interactions in cellular ffa assimilation. A further goal is to systemically investigate the manner in which
FABP modulates intracellular ffa transport. The studies will
examine and compare and the transfer kinetics of ffa from model
membranes and subcellular membranes to FABP, and from FABP to
membranes, and will elucidate the precise role of FABP in inter-
membrane ffa transfer in the enterocyte. An understanding of ffa assimilation at the molecular level will
enable more effective treatment of several pathophysiological and
drug-induced malabsorption syndromes, and will support the
continued development of oral drug delivery systems.
StatusActive
Effective start/end date5/1/871/31/21

Funding

  • National Institutes of Health: $264,910.00
  • National Institutes of Health: $61,800.00
  • National Institutes of Health: $12,932.00
  • National Institutes of Health
  • National Institutes of Health: $189,523.00
  • National Institutes of Health: $225,425.00
  • National Institutes of Health: $66,069.00
  • National Institutes of Health: $52,045.00
  • National Institutes of Health: $74,640.00
  • National Institutes of Health: $362,805.00
  • National Institutes of Health: $240,582.00
  • National Institutes of Health
  • National Institutes of Health: $398,684.00
  • National Institutes of Health: $460,126.00
  • National Institutes of Health: $286,520.00
  • National Institutes of Health: $391,908.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $389,109.00
  • National Institutes of Health: $266,796.00
  • National Institutes of Health: $351,808.00
  • National Institutes of Health: $14,305.00
  • National Institutes of Health
  • National Institutes of Health: $10,360.00
  • National Institutes of Health: $290,394.00
  • National Institutes of Health: $41,522.00
  • National Institutes of Health
  • National Institutes of Health: $233,576.00
  • National Institutes of Health: $295,194.00
  • National Institutes of Health: $354,424.00
  • National Institutes of Health: $336,966.00
  • National Institutes of Health: $324,095.00
  • National Institutes of Health: $106,505.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $386,038.00
  • National Institutes of Health: $337,159.00
  • National Institutes of Health: $144,470.00
  • National Institutes of Health
  • National Institutes of Health: $31,317.00
  • National Institutes of Health: $284,862.00
  • National Institutes of Health: $100,000.00
  • National Institutes of Health
  • National Institutes of Health: $51,800.00

ASJC

  • Medicine(all)

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