Genetic and Sex-Specific Transgenerational Effects of a High Fat Diet in Drosophila melanogaster

Abstract

An organism's phenotype is the product of its environment and genotype, but an ancestor’s environment can also be a contributing factor. The recent increase in caloric intake and decrease in physical activity of developed nations' populations is contributing to deteriorating health and making the study of the longer term impacts of a changing lifestyle a priority. The dietary habits of ancestors have been shown to affect phenotype in several organisms, including humans, mice, and the fruit fly. Whether the ancestral dietary effect is purely environmental or if there is a genetic interaction with the environment passed down for multiple generations, has not been determined previously. Here we used the fruit fly, Drosophila melanogaster, to investigate the genetic, sex-specific, and environmental effects of a high fat diet for three generations’ on pupal body weights across ten genotypes. We also tested for genotype-specific transgenerational effects on metabolic pools and egg size across three genotypes. We showed that there were substantial differences in transgenerational responses to ancestral diet between genotypes and sexes through both first and second descendant generations. Additionally, there were differences in phenotypes between maternally and paternally inherited dietary effects. We also found a treated organism’s reaction to a high fat diet was not a consistent predictor of its untreated descendants’ phenotype. The implication of these results is that, given our interest in understanding and preventing metabolic diseases like obesity, we need to consider the contribution of ancestral environmental experiences. However, we need to be cautious when drawing population-level generalization from small studies because transgenerational effects are likely to exhibit substantial sex and genotype specificity.

Lineage- and Sex-Dependent Behavioral and Biochemical Transgenerational Consequences of Developmental Exposure to Lead, Prenatal Stress, and Combined Lead and Prenatal Stress in Mice

“…Importantly, these effects were seen even with full outbreeding using unexposed C57BL/6J mice, compared with transgenerational studies where treated animals are bred to each other. Although differences by sex in F3 consequences are certainly recognized (Dew-Budd et al 2016;Zizzari et al 2016), the contribution of lineage transfer in relation to sex, and potential dynamic changes in response to ongoing environmental conditions, have received far less attention (Burggren 2015).…”

Ancestral diet leads to dynamic transgenerational plasticity for five generations in Drosophila melanogaster

“…To date, most studies documenting ancestral dietary modifications on offspring response only focus on a single extreme modification (e.g. a high-fat diet, a high-sugar diet, or a protein-restricted diet) (Zambrano et al, 2005, Benyshek et al, 2006, Dunn and Bale, 2011, Matzkin et al, 2013, Dew-Budd et al, 2016, Ost et al, 2014, Hoile et al, 2011). To better understand whether varying concentrations of the same ancestral dietary modification can lead to similar transgenerational responses, we compared the transgenerational responses of the three ancestral dietary sugar concentrations in flies.…”

“…While some evidence exists for the transmission of stable effects in the literature (Remy, 2010, Rechavi et al, 2014, Ashe et al, 2012), the fluctuating responses found in our study generally do not appear to match with these findings. Conversely, delayed and diminishing responses are quite common for transgenerational studies (J Marshall and Uller, 2007, Gluckman et al, 2005, Nystrand et al, 2016, Xia and De Belle, 2016, Dew-Budd et al, 2016, Buescher et al, 2013, Dunn and Bale, 2011, Pentinat et al, 2010, Franklin et al, 2010, Walsh et al, 2015). Unfortunately, these aforementioned interpretations are frequently based on studies with short-time scales and single-exposure changes, limiting the scope of inference.…”

“…transgenerational phenotypic plasticity) (Bonduriansky, 2012, Jablonka and Raz, 2009, Uller, 2008), which has been found to occur across a range of organisms (Xu et al, 2014, Tracey et al, 2013, Chamorro-Garcia et al, 2013, Valtonen et al, 2012, Rechavi et al, 2011, Painter et al, 2008). When ancestral experience affects offspring responses at least two or three generations after exposure, where the specific number of generations analyzed depends on the species’ reproductive strategy (namely when germ-line cells differentiate in development) (Buescher et al, 2013, Dew-Budd et al, 2016, Xia and De Belle, 2016, Dunn and Bale, 2011, Tauffenberger and Parker, 2014, Benyshek et al, 2006, Skinner, 2008), these effects are considered transgenerational.…”

Drosophilaas a model to study obesity and metabolic disease

“…Reproduction also requires tight control of lipid homeostasis. Although females must increase oocyte and whole-animal lipogenesis to support the production of offspring (Sieber and Spradling, 2015), morbid maternal obesity adversely affects egg size, glycogen and TAG content, adult mass and gene expression in offspring and even in the F2 generation (Buescher et al, 2013;Dew-Budd et al, 2016;Matzkin et al, 2013). Highly obesogenic diets reduce fecundity (Brookheart et al, 2017;Matzkin et al, 2013Matzkin et al, , 2011 as does genetically induced obesity (Palu et al, 2017).…”