|
Diet changes gene expression and physiology
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 Albertha J.M. 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 their paper: "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.
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."
Lesley MacNeil, PhD,
Postdoctoral student, Walhout Lab
University of Massachusetts Medical School
first author on the paper.
Strikingly, Walhout and colleagues observed that even when fed a small amount of the Comamonas bacteria in a diet otherwise comprised 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.
"It's just as true that a small amount of a 'healthy' food in an otherwise unhealthy diet could elicit a beneficial change in gene expression that could have profound physiological effects," said Walhout.
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 their paper, "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 led to metabolic imbalances that interfered with the animal's dietary response—a result that may have a direct connection 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 second Cell 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 that genetic
regulation rapidly facilitates internal response to
physiologic and external environmental cues in order
to maintain metabolic balance in the worm.
Interestingly, a similar phenomenon is involved in
mutations leading to genetic metabolic diseases in humans.
Classes of genetic diseases result 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, 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."
About the University of Massachusetts Medical School
The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $250 million in research funding annually, 80 percent of which comes from federal funding sources. The mission of the Medical School is to advance the health and well-being of the people of the commonwealth and the world through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care. For more information, visit http://www.umassmed.edu.
Original article: http://blog.smu.edu/research/2013/03/25/fruit-flies-fed-organic-diets-are-healthier-than-flies-fed-nonorganic-diets-study-finds/
|
Home- - -History-- -Bibliography- -Pregnancy Timeline- --Prescription Drugs in Pregnancy- -- Pregnancy Calculator- --Female Reproductive System- News Alerts -Contact
Commons License.
