120 Introduction to Human Nutrition
the concept of genetic susceptibility to diet (Table
6.7).
Modulation of gene expression
Dietary fatty acids and/or their intracellular (eico-
sanoid) derivatives can also infl uence the expression
of genes (rate of gene transcription) by interacting
with specifi c nuclear receptors within the nucleus of
cells. These nuclear receptors control the rate of gene
transcription by binding to specifi c regions of DNA
known as responsive elements. Genes associated with
the production of functional proteins can be either
stimulated or repressed according to the nature of the
nuclear transcription factor and its binding substrate
(PUFAs or derivative). Peroxisome proliferator-acti-
vated receptors (PPARs) represent examples of nuclear
receptors that may utilize long-chain PUFAs as sub-
strates. PPARs can be found in all tissues of the body,
but notably in the liver, where they control the syn-
thesis of lipid and apoproteins (PPAR-α), and in
adipose tissue (PPAR-γ), where they control the dif-
ferentiation of adipocytes and insulin-sensitive mobi-
lization and synthesis of TAG. SREBPs represent
another example of nuclear transcription proteins
that control cholesterol and fatty acid metabolism
within the cell.
6.12 Perspectives on the future
Future research on fatty acids and their role in health
and disease will be largely dictated by progress in
intervention studies using fatty acid supplements in
chronic diseases of infl ammation, brain degeneration,
cancer, and heart disease. Some of these studies will
be based on effects of dietary fats on gene expression
that have yet to be discovered; others will be based on
information that we already have. No doubt the search
for the “ideal” fat intake will continue, but this seems
misguided because humans in good health in differ-
ent cultures and geographical locations ultimately
consume a wide range of total fat and fatty acid ratios;
their overall health is based on much more than their
fat intake. Nevertheless, pursuit of an ideal fat intake
or composition will satisfy the thirst of many research-
ers, consumers, and government agencies but, in all
likelihood, will not greatly alter the impact of fats on
disease processes. These would include:
● the role of the quantity and quality of dietary fat on
postprandial lipemia, specifi c lipoproteins, and the
risk of CHD
● the metabolic roles of the short-chain fatty acids
(1–6 carbons)
● the effect of trans fatty acids in baby foods, and the
level of intake of trans fatty acids that will increase
the risk of CHD in adults
● the appropriate amounts of n-6 to n-3 polyunsatu-
rates to prevent, reverse, and/or treat chronic
degenerative diseases
● the requirements of docosahexaenoate and other
long-chain PUFA in infant and enteral feeding
● the conditional indispensability of particular fatty
acids throughout the life cycle (especially during
pregnancy and lactation, and in the aged)
● the effects of particular dietary fatty acids and com-
binations of fatty acids on hormone and gene
expression.
More knowledge in all of these areas will lead to a
better understanding of the mechanisms through
which dietary lipids infl uence blood lipids and lipo-
proteins and therefore the risk of chronic diseases. It
will also lead to improved recommendations regard-
ing the quantity and quality of dietary fats that are
commensurate with optimum human health.Table 6.7 Effect of apoprotein E phenotype on serum cholesterol
Phenotype (gene frequency) Receptor binding affi nity Hepatic free cholesterol LDL receptor activity LDL-C
E4 (ε 4 15%) + + +↑ (feedback) ↓↑
E3 (ε 3 77%) + + →→→
E2 (ε 2 8%) + ↓ (feedback) ↑↓
Carriage of ε 4 allele is associated with increased risk of coronary heart disease and greater changes in low-density lipoprotein cholesterol (LDL-C)
in response to increased dietary fat and cholesterol in men.