Genotype-by-Diet Interactions Drive Metabolic Phenotype Variation inDrosophila melanogaster

Abstract

The rising prevalence of complex disease suggests that alterations to the human environment are increasing the proportion of individuals who exceed a threshold of liability. This might be due either to a global shift in the population mean of underlying contributing traits, or to increased variance of such underlying endophenotypes (such as body weight). To contrast these quantitative genetic mechanisms with respect to weight gain, we have quantified the effect of dietary perturbation on metabolic traits in 146 inbred lines of Drosophila melanogaster and show that genotype-by-diet interactions are pervasive. For several metabolic traits, genotype-by-diet interactions account for far more variance (between 12 and 17%) than diet alone (1-2%), and in some cases have as large an effect as genetics alone (11-23%). Substantial dew point effects were also observed. Larval foraging behavior was found to be a quantitative trait exhibiting significant genetic variation for path length (P ¼ 0.0004). Metabolic and fitness traits exhibited a complex correlation structure, and there was evidence of selection minimizing weight under laboratory conditions. In addition, a high fat diet significantly increases population variance in metabolic phenotypes, suggesting decreased robustness in the face of dietary perturbation. Changes in metabolic trait mean and variance in response to diet indicates that shifts in both population mean and variance in underlying traits could contribute to increases in complex disease.

Drosophilaas a model to study obesity and metabolic disease

“…One can also assess the ability to survive on and process high-calorie obesogenic diets, or the degree of 'obesity tolerance'. Like humans, some obese flies can be quite healthy , whereas other genotypes develop severe effects with only modest levels of overfeeding Nakagami et al, 2003;Teesalu et al, 2017 wild-caught Drosophila strains exhibited various degrees of dietdependent obesity, consistent with a model where fat storage represents a balance between optimizing storage depots and overloading the animal (Reed et al, 2014(Reed et al, , 2010.…”

“…For high-carbohydrate feeding, high-sucrose diets are the most common (Buescher et al, 2013;Garrido et al, 2015;Havula et al, 2013;Navrotskaya et al, 2016;Musselman et al, 2011;Pasco and Léopold, 2012;Reis, 2016;Rovenko et al, 2015a); however, highglucose and high-fructose diets have also been used (Rovenko et al, 2015b). For high-fat feeding, coconut oil supplementation is the most common way to elicit diet-induced obesity in flies (Birse et al, 2010;Heinrichsen et al, 2014;Hong et al, 2016;Reed et al, 2010), although lard and the hydrogenated soybean and palm oil product known as Crisco have also been used (Lee et al, 2017;Musselman et al, 2011;Woodcock et al, 2015). The formulation of these diets can be tricky and care must be taken to avoid reduced survival owing to unusually sticky or dry food conditions.…”

“…Collections of laboratory-generated and naturally occurring genetic variants isolated from all over the world make Drosophila an ideal model in which to test the effects of genes on obesity (Reed et al, 2010;Reis et al, 2010, among others). Genetic screens using these and other resources have identified genes that confer obesity in Drosophila via TAG quantification or buoyancy screening (Baumbach et al, 2014a;Lee et al, 2014;Mosher et al, 2015;Reis et al, 2010).…”

Role of Fat Body Lipogenesis in Protection against the Effects of Caloric Overload in Drosophila

“…More recently, caloric excess has been shown to elicit many of the same negative consequences in model organisms as have long been observed in humans (1)(2)(3)(4)(5)(6)(7). Work from our laboratory and that of others has shown that feeding Drosophila a high sugar diet (HSD) 2 results in a model of type 2 diabetes (T2D) that includes hyperglycemia, obesity, insulin resistance, cardiac arrhythmias, and reduced lifespan (4,8,73).…”

Genotype and environment shape the fitness of Drosophila melanogaster

“…However, under local adaptations, heterogenous environments and genotype-by-environment interactions may maintain a balanced genetic variation (Fanara et al, 2006;Lazzaro et al, 2008). In genotype-by-environment interactions, the genotypes may express different levels of the phenotype by the action of environmental factors (Reed et al, 2010).…”