Address for correspondence: Steven D. Clarke, Ph.D., M. M. Love Chair of Nutritional, Cellular, and Molecular Sciences, 117 Gearing Building, University of Texas at Austin, Austin, TX 78712. Fax: 512-232-5864.
stevedclarke{at}mail.utexas.edu
Ann. N.Y. Acad. Sci. 967: 283-298 (2002).
The development of obesity and associated insulin resistance
involves a multitude of gene products, including proteins involved
in lipid synthesis and oxidation, thermogenesis, and cell differentiation.
The genes encoding these proteins are in essence the blueprints
that we have inherited from our parents. However, what determines
the way in which blueprints are interpreted is largely dictated
by a collection of environmental factors. The nutrients we consume
are among the most influential of these environmental factors.
During the early stages of evolutionary development, nutrients
functioned as primitive hormonal signals that allowed the early
organisms to turn on pathways of synthesis or storage during
periods of nutrient deprivation or excess. As single-cell organisms
evolved into complex life forms, nutrients continued to be environmental
factors that interacted with hormonal signals to govern the
expression of genes encoding proteins involved in energy metabolism,
cell differentiation, and cell growth. Nutrients govern the
tissue content and activity of different proteins by functioning
as regulators of gene transcription, nuclear RNA processing,
mRNA degradation, and mRNA translation, as well as functioning
as posttranslational modifiers of proteins. One dietary constituent
that has a strong influence on cell differentiation, growth,
and metabolism is fat. The fatty acid component of dietary lipid
not only influences hormonal signaling events by modifying membrane
lipid composition, but fatty acids have a very strong direct
influence on the molecular events that govern gene expression.
In this review, we discuss the influence that (n-9), (n-6),
and (n-3) fatty acids exert on gene expression in the liver
and skeletal muscle and the impact this has on intra- and interorgan
partitioning of metabolic fuels.
