Transgenerational Obesity and Healthy Aging in Drosophila

Abstract

Substantial evidence suggests that individuals born to overweight and obese parents suffer detrimental health consequences that dramatically decrease healthy aging. The number of obese individuals worldwide now exceeds the number of under- and malnourished individuals. This obesity epidemic is responsible for approximately 4 million deaths worldwide each year, and predisposes sufferers to a range of age-related diseases such as cardiovascular diseases, and metabolic syndrome. Additionally, obesity is associated with an accelerated onset of age-related ailments, such as cancers and inflammation. The importance of dietary interventions to reduce the incidence of obesity is magnified by emerging evidence that parental physiology can predispose future generations to poor health outcomes. Characterizing and understanding these effects, and how they are mediated, is important if we are to continue to drive improvements to population health. In this article, we synthesize evidence for the intergenerational and transgenerational phenotypic effects of parental obesity. We concentrate on how the fruit fly Drosophila melanogaster can be used as a model to study these effects. Fruit flies are highly tractable, and their conserved nutrient signaling and metabolic pathways make them an ideal model for studying nutritional effects on metabolic, reproductive, and aging phenotypes.

Maternal and paternal sugar consumption interact to modify offspring life history and physiology

“…Exploration of effects beyond the F1 would facilitate interpretation of whether the patterns reported here are more likely mediated by direct condition-transfer from parents to offspring, or via epigenetic mechanisms that are more likely to be anticipatory in nature (Sánchez-Tójar et al, 2020). Finally, we note that the insights gained here from the study of fruit flies may have relevance to mechanisms underpinning nutritional programming in mammalian systems including humans, given that many of the genes and metabolic pathways involved in nutrition, obesity, and aging are generally conserved (Camilleri-Carter et al, 2019).…”

“…Dietary variation affects a wide range of fitness related traits-from physiological measures of obesity, to reproductive success, and lifespan (Duxbury & Chapman, 2020). Many of these effects appear to be conserved across invertebrates and vertebrates, and modifications to diet in one generation have been shown to trigger indirect effects on the metabolic performance and body composition of offspring and grand offspring (Camilleri-Carter, Dowling, Robker, & Piper, 2019;Dunn & Bale, 2009;Ivimey-Cook et al, 2020). Research into dietary-mediated intergenerational inheritance has focussed on mice and flies, where studies have explored the intergenerational consequences of obesogenic diets.…”

Diet’s impact dictated by synonymous mitochondrial SNP interacting with nucleotype

“…Diet can modulate fitness by effects that span one or more generations (Camilleri-Carter et al, 2019; Deas et al, 2019; Öst et al, 2014; Rivera et al, 2015). We are not aware of a prior demonstration of genetic variation in such transgenerational reprogramming, nor of whether it is subject specifically to mito-nuclear variation.…”

Exploring the evidence for epigenetic regulation of environmental influences on child health across generations

“…Obesity. In animal models of rats and mice, maternal prenatal nutrition has been shown to influence offspring development and long-term health, including body size, obesity, and related metabolic disorders [147][148][149] , although the mechanisms remain unclear 10,150,151 . Consumption of a high-fat diet during Fig.…”