Research condensed into 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, examine how physiology and metabolism are connected to diet. A transparent roundworm was used as the model organism and different diets produced differences in gene expression in the worm that were 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.”
At least 87 changes in gene expression were identified when the two diets were compared. These changes were independent of the TOR and insulin signaling pathways, which are the pathways typically active in nutritional control.
Instead, the changes occur in the genetic pathway 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.”
The research points to the possibility that specific quantities of certain foods may be optimal under different conditions and for promoting physiological outcomes. How this research is translated into human physiology remains to be seen.
“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.
The Walhout lab explored the possibility of using the worm model to answer 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 her research colleagues found that disrupting gene expression involved with the worm model 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 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 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.
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