Food Lipids: Chemistry, Nutrition, and Biotechnology

esponsible, at least in part, for the reduced eicosanoid levels (67). CLA could also
affect the lipoxygenase pathway to reduce product formation. Cunningham et al. (61)
showed that the addition of CLA and NDGA to MCF-7 cells resulted in synergistic
growth suppression, suggesting that CLA effects were mediated through lipoxygenase
inhibition.
The effect of dietary CLA on eicosanoid metabolism could be twofold. First,
CLA isomers could directly compete with substrate concentration and activity or
expression of cyclooxygenase or lipoxygenase. Second, CLA could be further desaturated
and elongated to its 20-carbon equivalent and exert its effect by competing
with other 20-carbon fatty acids, mainly arachidonic acid and eicosapentaenoic acid,
to reduce the production of their corresponding eicosanoids. Experiments to evaluate
the effects of CLA isomers on eicosanoid biosynthesis have not yet been conducted.
We hypothesized that CLA depressed arachidonate-derived eicosanoid biosynthesis
since dietary sources consistently reduced ex vivo PGE 2 production in rat bone organ
culture and liver homogenate (74). The reduction in PGE 2 by CLA might be explained
as a competitive inhibition of n-6 PUFA formation that results in lowered
substrate availability of cyclooxygenase. Although there was a trend of reduced arachidonic
acid concentration in bone tissues, the dramatic decrease in ex vivo PGE 2
production in bone organ culture could not be satisfactorily explained by a lack of
substrate (74).
The biosynthesis of PGE 2 in bone (cells of the osteoblast lineage) is highly
regulated by local and systemic factors (122–124). Fatty acids have been shown to
modulate the expression and activity of this key enzyme. For example, Nanji et al.
(125) showed that saturated fat reduced peroxidation and decreased the levels of
COX-2, the inducible form of COX, in rat liver. In a rat dietary study on colon
tumorigenesis, a high-fat corn oil diet (rich in n-6 fatty acids) up-regulated COX-2
expression, but a high-fat fish oil diet (rich in n-3 fatty acids) inhibited it; however,
expression of COX-1, the constitutive enzyme, was not affected (126). We speculate
that CLA may influence PGE 2 production through the COX enzyme system, more
likely on COX-2, to exert its physiological effects in bone and other tissues to
influence bone metabolism as well as cancer.
Sebedio et al. (105) reported that CLA may be further desaturated and elongated
to form conjugated 20:4 isomers that might block the access of arachidonic
acid to COX. The unusual 20:4 isomers derived from CLA might also affect the
activity of the COX enzymes. Further study with CLA is needed to confirm if its
isomeric analogs alter COX activity and expression as a primary mechanism of action
and potential role in controlling cancer and inflammatory disease.
The isomers of CLA were shown to modulate the expression and activity of
cytokines and growth factors. Buison et al. (127) reported that 1% CLA in a 40%
(wt/wt) fat diet lowered circulating IGF-I level in obese female Wistar rats. We
reported that dietary CLA lowered basal and lipopolysaccharide (LPS) stimulated
interleukin-6 production and basal tumor necrosis factor production by resident peritoneal
macrophages in rats (68). Furthermore, CLA reduced the release of LTB 4 (67),
a strong bone resorption factor (128), from peritoneal exudate cells and splenic cells
in response to the dietary CLA levels. Assuming that CLA would have similar effects
on these cytokines in bone, together with the fact that CLA reduced the production
of PGE 2 in bone tissue, one could hypothesize that a proper dietary level, the anti-
Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.