Transgenerational Inheritance of Metabolic State in Drosophila. Rebecca A. Somer, Carl S. Thummel. Human Genetics, University of Utah School of Medicine, Salt Lake City, UT.

   Poor nutrition has been implicated as a key causal factor in the development of metabolic syndrome. Recent data, however, has suggested that poor nutrition and the resulting altered metabolic state in the parental generation can also have a dramatic impact on the health of subsequent generations. Several human studies have shown that nutrient deprivation, gestational diabetes, and obesity have an effect on the metabolic state of children at both adolescence and adulthood. In addition, studies in rodents have shown that the adult progeny of mothers subjected to nutrient depletion display hallmarks of obesity and diabetes. Similar results are seen in the progeny of male mice fed a low protein diet, along with changes in the expression of genes involved in lipid metabolism (Carone et al 2010 Cell). These results suggest that the inheritance of a metabolic program is more than a gestational effect. At best, however, these studies are correlative, and the mechanism of the inheritance of metabolic state is still unknown. To determine if parental metabolism influences progeny metabolism in Drosophila, we have used a combination of dietary and genetic methods to alter the parental metabolic state while maintaining a constant environment for subsequent generations. Our preliminary studies reveal changes in the metabolite levels of adult progeny when the parental generation is subjected to a dietary or genetic metabolic insult as compared to the progeny of control parents. We propose that these changes indicate that the progeny are inheriting an altered metabolic program in order to adapt to a new nutritional environment. This data provide a foundation to characterize the genetic and molecular mechanisms underlying the transgenerational inheritance of metabolic state in an easily manipulable genetic system.