EFFECTS OF DIETARY LINOLENATE ON ARACHIDONATE

  • Hwang, Daniel H (PI)

Project: Research project

Project Details

Description

The objective of the proposed study is to evaluate the efficacy of dietary
linolenic acid (18:3n-3), as compared to eicosapentaenoic acid (20:5n-3) or
docosahexaenoic acid (22:6n-3) which are abundant in fish oil, to inhibit
the formation of eicosanoids derives from arachidonic acid (20:4n-6) in rat
tissues. The suggested beneficial effects of 20:5n-3 in reducing
thrombogenic potential are considered to be primarily due to its
competitive inhibition of the conversion of 20:4n-6 to thromboxane A2
(TXA2), and reduction of the 20:4n-6 level in platelets by displacement.
An important question can be raised as to whether another type of dietary
n-3 fatty acid can achieve similar or even more beneficial effects than
20:5n-3. This applicant proposes that dietary 18:3n-3 inhibits the
conversion of linoleic acid (18:3n-6) to 20:4n-6. It also inhibits the
formation of cyclooxygenase-derived products of 20:4n-6. Furthermore,
18:3n-3 is not a substrate for leukotrienes (LT), whereas 20:5n-3 is a
preferred substrate for 5-lipoxygenase leading to the formation of pentaene
LTs. Thus, dietary 18:3n-3 may be a more effective inhibitor than 20:5n-
3 for the biosynthesis of LTs. The specific aim is to compare 18:3n-3 with
20:5n-3 or 22:6n-3 for its effects on: (1) levels of eicosanoid precursor
acids in free fatty acid fractions and tissue phospholipids, and (2) the
formation of eicosanoids derived both from 20:4n-6 and 20:5n-3 in tissues.
Rats will be fed graded amounts of purified 18:3n-3, 20:5n-3 or 22:6n-3 in
the presence of a constant amount of 18:2n-6 for 12 weeks. Eicosanoids
synthesized in tissues will be determined by radioimmunoassay and
immunochromatographic assay. The long term objective is to establish the
desirable ratio of n-3 to n-6 fatty acids in our diets to reduce certain
risks of coronary heart disease. Presently, most dietary guidelines use
polyunsaturated fatty acids (PUFA) without differentiating types of PUFA
(n-3 or n-6). In the future, this ratio may need to be specified in the
dietary guidelines.
StatusFinished
Effective start/end date6/1/894/30/03

Funding

  • National Institutes of Health
  • National Institutes of Health: $85,260.00
  • National Institutes of Health: $185,627.00
  • National Institutes of Health: $179,366.00
  • National Institutes of Health: $191,169.00
  • National Institutes of Health
  • National Institutes of Health: $41,287.00
  • National Institutes of Health
  • National Institutes of Health: $165,828.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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