Even the Littlest
Bites: Dietary Influences Tied to Changes in Gene Expression
Sometimes
you just can't resist a tiny piece of chocolate cake. Even the most
health-conscious eaters find themselves indulging in junk foods from time to
time. New research by scientists at the University of Massachusetts Medical
School (UMMS) raises the striking possibility that even small amounts of these
occasional indulgences may produce significant changes in gene expression that
could negatively impact physiology and health.
A
pair of papers published in Cell by A.J. Marian Walhout, PhD,
co-director of the Program in Systems Biology and professor of molecular
medicine at UMMS, describe how metabolism and physiology are connected to diet.
Using C. elegans, a transparent roundworm often used as a model
organism in genetic studies, Dr. Walhout and colleagues observed how different
diets produce differences in gene expression in the worm that can then be
linked to crucial physiological changes.
"In short, we found that when C. elegans are fed diets of different types of bacteria, they respond by dramatically changing their gene expression program, leading to important changes in physiology," said Walhout. "Worms fed a natural diet of Comamonas bacteria have fewer offspring, live shorter and develop faster compared to worms fed the standard laboratory diet of E. coli bacteria."
Walhout
and colleagues identified at least 87 changes in C. elegans gene
expression between the two diets. Surprisingly, these changes were independent
of the TOR and insulin signaling pathways, gene expression programs typically
active in nutritional control.
Instead, the changes occur, at least in part, in
a regulator that controls molting, a gene program that determines development
and growth in the worm. This connection provided one of the critical links
between diet, gene expression and physiology detailed in "Diet-induced
Development Acceleration Independent of TOR and Insulin in C. elegans."
"Importantly, these same regulators that are influenced by diet in the
worms control circadian rhythm in humans," said Lesley MacNeil, PhD, a
postdoctoral student in the Walhout Lab and first author on the paper. "We
already know that circadian rhythms are affected by diet. This points to the
real possibility that we can now use C. elegans to study the
complex connections between diet, gene expression and physiology and their relation
to human disease."
Strikingly,
Walhout and colleagues observed that even when fed a small amount of the Comamonas bacteria
in a diet otherwise composed of E. coli bacteria, C.
elegans exhibited dramatic changes in gene expression and physiology.
These results provide the tantalizing possibility that different diets are not
"healthy" or "unhealthy" but that specific quantities of
certain foods may be optimal under different conditions and for promoting
different physiological outcomes.
Additional
research by the Walhout Lab further explored the possibility of using C.
elegans as a model system to answer complex questions about disease
and dietary treatment in humans. Detailed in the "Integration of Metabolic
and Gene Regulatory Networks Modulates the C. elegans Dietary
Response," Walhout and colleagues found that disrupting gene expression
involved with C. elegans metabolism lead to metabolic
imbalances that interfered with the animal's dietary response; a result that
may have a direct correlation to the treatment of a class of human genetic
diseases.
"To
better understand the molecular mechanisms by which diet effects gene
expression in the worm, we performed complimentary genetic screens looking for
genes that gave an abnormal response to diet," said Emma Watson, a
doctoral student in the Walhout Lab and co-first author on the secondCell study
together with Dr. MacNeil.
"What we discovered was a large network of
metabolic and regulator genes that can integrate internal cellular nutritional
needs and imbalances with external availability," said Watson. "This
information is then communicated to information processing genes in the worm to
illicit the appropriate response in the animal."
These
findings suggest the existence of a genetic regulatory network that facilitates
rapid responses to internal physiological and external environmental cues in
order to maintain a metabolic balance in the worm.
Interestingly, a similar
phenomenon is involved in mutations that lead to inborn metabolic diseases in
humans; classes of genetic diseases resulting from defects in genes that code
for enzymes which help convert nutrients into usable materials in the cell.
These diseases are usually treated by dietary interventions designed to avoid
build-up of toxins and to supplement patients with metabolites that may be
depleted.
According
to Dr. Walhout, it may be possible to use this genetic regulatory network
in C. elegans to compare how certain dietary regimens can be
used to mitigate these metabolic diseases. It may also be used to screen for
drugs or other small molecules that can produce the same results as dietary
treatments.
Though
Walhout and colleagues started out asking a fundamental dietary question in the
worm, what they got was an answer directly related to disease and treatment in
humans, thus establishing C. elegans as a model system for
elucidating the mechanisms for dietary responses, inborn metabolic diseases and
the connections between them.
"It's
very hard to answer questions about the complex interaction between diet, gene
expression and physiology in humans for many reasons," said Walhout.
"Now, we can use a very tractable system -- namely C. elegans --
to ask precise questions about which components in diet can effect gene
expression and physiological traits and ultimately disease, in humans."
Story Source:
The
above story is reprinted from materials provided by University of Massachusetts Medical
School. The original article was written by Jim Fessenden.
Note: Materials may be edited for content and length. For further
information, please contact the source cited above.
Journal Reference:
1. Lesley T. MacNeil, Emma Watson,
H. Efsun Arda, Lihua Julie Zhu, Albertha J.M. Walhout. Diet-Induced
Developmental Acceleration Independent of TOR and Insulin in C. elegans. Cell,
2013; 153 (1): 240 DOI:10.1016/j.cell.2013.02.049
