Food Lipids: Chemistry, Nutrition, and Biotechnology

Mice fed triolean or a fat-free diet exhibited marked increases in hepatic �5 desaturase
mRNA expression relative to mice fed safflower oil or fish oil [32].
Although the metabolism of n-3 and n-6, and even n-9, fatty acids in animals
is thought to utilize the same �6 and �5 enzymes, there are specific differences in
the desaturation efficiencies with regard to substrate. For instance, the most abundant
n-6 fatty acids in animals are clearly linoleic and arachidonic acids. In contrast, the
only n-3 fatty acid present at concentrations commensurate with these n-6 fatty acids
is DHA, despite the fact that most dietary n-3 fatty acid exists as linolenic acid
(18:3n-3). There is also the virtual nonexistence of �6 and �5 desaturase products
of endogenously produced or dietary oleic acid (18:1n-9) in animals. Clearly, the
families of fatty acids are not simple competitors with each other for desaturation
and there must exist a complex regulation of desaturation. The availability of clones
for the �5 and �6 desaturase genes heralds a truly exciting and productive future
for understanding the role of PUFA metabolism in physiology and nutrition.
5. Regulation of Desaturase Activity
The regulation of desaturase activity is complex and appears to involve a number
of signals. The activities of mammalian desaturating enzyme systems are sensitive
to several metabolic signals [35–39]. These various effectors cause an inhibition
in the net desaturation through the �6 and �5 enzymes. Stearoyl CoA desaturase
activity is substantially suppressed in the fasted state [40] and is restored by refeeding
or insulin administration. In culture, scd2 gene expression was suppressed by cholesterol
[41]. However, in rats, scd expression was induced by dietary cholesterol
[42]. The regulation of SCD by PUFAs and cholesterol was reviewed by Ntambi
[13].
As direct effects, the desaturases are strongly inhibited by their products; hence,
diets rich in PUFAs tend to suppress desaturase activity. Strikingly, fasting also
decreases �6 desaturation, and a basic protocol of fasting and refeeding accelerates
essential fatty acid deficiency [43].
Endocrine signaling has been variously reported to affect desaturation [35,
43,44]. Glucagon, epinephrine, corticoids, and thyroxine all lower the activity of the
�6 and �5 desaturases [43]. Diabetes in humans and in animal models is associated
with lower concentrations of PUFAs, and this is paralleled by measurable decreases
in the activity of the �6 and �5 desaturases. Consistently, insulin administration
restores the desaturase activities in both humans and in animal models of diabetes
and normalizes the content of PUFAs in membranes. As an illustration of the extent
of control of these systems, insulin does not increase desaturation in normal individuals
[45].
In studies designed to examine the mechanisms of modulatory effects, cAMP
was implicated as causal to desaturase modification, and the effect can be mimicked
by dibutryl cAMP both in vivo [46] and in vitro [47]. Interestingly, corticosteroids
and thyroxine depress both �6 and �5 desaturase activities but increase the �9
desaturase activity [35,48].
To date there is a paucity of metabolic systems in which the apparent activity
of the �5 and �6 desaturases increases over controls. Growth hormone strongly
induces both the �6 and �5 enzyme activities and their metabolic products [25,49].
Growth hormone also substantially down-regulates the transcription of the stearoyl
CoA desaturase of liver and adipose.
Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.