Diet Composition Differentially Affects Insulin Pathway Compromised and Control Flies

Abstract

The insulin pathway is an anabolic pathway that controls, amongst other things, glucose homeostasis. It is an evolutionarily conserved pathway. Disruptions in insulin pathway functions can lead to diabetic states. Diabetes, a very common occurrence in modern life, afflicts a significant portion of the population of developed and developing countries worldwide. Yet, few studies have addressed the evolution of diabetic states on a long-term basis. Here, we cultured three different insulin pathway signaling compromised flies (heteroallelic mutant combinations, akin to diabetes mellitus type II) and wild type control flies, for the extent of one generation in different isocaloric diets fed at libitum, with or without extra methionine added. All fly stocks have a homogenized genetic background. We measured weight, total lipid, and carbohydrate content of adults at two different time points, and survival of adults reared in some of the different diets. Results show that, despite the fact that all diet regimes allow survival of at least a fraction of flies to adulthood, life histories are significantly different. Higher protein content diets promote better survival compared to higher percentage lipid and carbohydrate diets, and added methionine promotes survival in moderately reduced protein content diets. In mutants, survival is significantly reduced, and added methionine generally has an effect, albeit a more modest one. Our results highlight the value of higher percentage protein diets, and differences in effects in “healthy” versus “diabetic” states. They also show that added methionine, proposed as a “sensor” for protein content in food for flies, leads to differential effects depending on the adequacy of the diet regime.