Food Lipids: Chemistry, Nutrition, and Biotechnology

Jump and Clarke (136) and Clarke (137)] and a coordinate induction of genes encoding
proteins involved in lipid oxidation and thermogenesis (discussed in Sect.
IV.C below). PUFA regulation of lipogenic genes is mediated at both the transcriptional
level, as for pyruvate kinase, pyruvate dehydrogenase, acetyl CoA carboxylase,
and fatty acid synthase, as well as the posttranscriptional level, as for glucose-6phosphate
dehydrogenase [see reviews by Jump and Clarke (136) and Clarke (137)].
There is emerging evidence that the PUFA-induced suppression of lipogenic enzymes
is mediated by changes in the expression and cellular localization of the transcription
factor, sterol regulatory element–binding protein 1 (SREBP-1) (147,149,150). Overexpression
of this transcription factor in the liver leads to a marked elevation in the
mRNAs encoding several lipogenic enzymes and to very high rates of de novo
lipogenesis (151,152). Consumption of diets containing n-6 (safflower oil) or n-3
(fish oil) fatty acids leads to a decrease in membrane content of SREBP-1 precursor
and nuclear content of SREBP and a concomitant reduction in lipogenic gene expression
in the liver (147). All effects are greater for the n-3- than the n-6-containing
diets (147). Most studies investigating the effects of n-3 fatty acids on SREBPs are
limited to lipogenic gene expression in the liver rather than adipose tissue. Whether
analogous regulatory processes govern n-3 fatty acid modulation of SREBPs and
lipogenic genes in adipose tissue is unknown. Consistent with the inhibitory action
of n-3 fatty acids on expression of genes involved in hepatic lipid metabolism, others
have observed similar effects in white adipose tissue (153,154). It is tempting to
speculate than n-3 fatty acids may also influence gene expression in adipose tissue
via regulation of SREBPs.
B. Influence of Dietary Fat on Lipid Uptake
Lipoprotein lipase (LPL) has been called the ‘‘gate keeper’’ enzyme because it controls
the rate of uptake of lipid by adipose cells (155). This enzyme is elevated in
association with genetic and diet-induced obesity in animals and humans. The ability
of n-3 polyunsaturated fatty acids to lower serum triglycerides is thought by some
to be due to an action on lipoprotein lipase. Several groups have reported an increase
in endogenous LPL activity and post-heparin LPL activity with n-3 fatty acid supplementation
in both healthy and hypertriglyceridemic patients (156,157) and experimental
animals (158). In contrast, others observed no effect of n-3 fatty acids on
LPL activity in humans (159,160) or rats (161). Raclot et al. (153) reported a reduction
in LPL expression in retroperitoneal fat depots, but not in subcutaneous fat
depots, in rats fed the n-3 fatty acid docosahexaenoic acid (DHA) alone or in combination
with the n-3 fatty acid eicosapentaenoic acid (EPA), suggesting site-specific
effects. In addition, LPL activity may not necessarily correspond to mRNA levels,
as posttranscriptional events, such as glycosylation and binding of LPL to cell surface
heparan sulfate proteoglycans, modulate expression and activity of the enzyme (162).
Furthermore, while alterations in LPL activity or expression may function in the
lowering of serum lipid levels associated with fish oil (n-3 fatty acid) consumption,
it is at odds with the finding of reduced adipose tissue mass in animals fed the same
diets. Conversely, the reduced obesity associated with diets high in n-3 polyunsaturated
fatty acids may be due to the influence of these fatty acids on reducing hepatic
fatty acid synthetase activity (158,163) and stimulating fatty acid oxidation (see
below).
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