Diet-induced insulin resistance & exercise in Drosophila melanogaster is highly influenced by genotype & sex

Abstract

Type 2 Diabetes, characterized by a combination of insulin resistance and impaired insulin secretion, is a serious metabolic disorder in humans that not only affects adults, but now young children. The model organism Drosophila melanogaster has emerged as an excellent model to study metabolic regulation. Using a high sucrose diet to induce insulin resistance, I used multiple fly lines to explore how genotype and sex interacts with the progression of insulin resistance and how exercise can influence this response. Flies were grouped and placed on one of four conditions: control diet (CD), high sucrose diet (HSD), control diet with exercise (CDEx), or high sucrose diet with exercise (HSDEx). Flies were exercised using a fly treadmill. Weight and various metabolites known to respond to diet and exercise were quantified, along with gene expression of various nodes in the insulin pathway. Twenty-five percent of fly lines on the HSD displayed symptoms of insulin resistance, such as hyperglycemia, glucose intolerance, and/or hyperinsulinemia, as well as patterns in insulin pathway gene expression that is indicative of insulin resistance. Flies experienced physiological changes in response to exercise, which changed 11-13% of the metabolome of each sex, and 20-29% of the metabolome of each line. Strikingly, across all experiments, fly response to diet and exercise was highly genotype and sex-dependent. This study demonstrates the complex nature of insulin resistance and most importantly, the importance of studying disease related states using multiple genetic backgrounds and both sexes.