Abstract
Obesity is one of the dramatic health issues affecting developed and developing nations, and exercise is a well-established intervention strategy. While exercise-by-genotype interactions have been shown in humans, overall little is known. Using the natural negative geotaxis of Drosophila melanogaster, an important model organism for the study of genetic interactions, a novel exercise machine, the TreadWheel, can be used to shed light on this interaction. The mechanism for inducing exercise with the TreadWheel is inherently gentle, thus minimizing possible confounding effects of other stressors. Using this machine, we were able to assess large cohorts of adult flies from eight genetic lines for their response to exercise after one week of training. We measured their triglyceride, glycerol, protein, glycogen, glucose content, and body weight, as well as their climbing ability and feeding behavior in response to exercise. Exercised flies showed decreased stored triglycerides, glycogen, and body weight, and increased stored protein and climbing ability. In addition to demonstrating an overall effect of TreadWheel exercise on flies, we found significant interactions of exercise with genotype, sex, or genotype-by-sex effects for most of the measured phenotypes. We also observed interaction effects between exercise, genotype, and tissue (abdomen or thorax) for metabolite profiles, and those differences can be partially linked to innate differences in the flies' persistence in maintaining activity during exercise bouts. In addition, we assessed gene expression levels for a panel of 13 genes known to be associated with respiratory fitness and found that many responded to exercise. With this study, we have established the TreadWheel as a useful tool to study the effect of exercise in flies, shown significant genotype-specific and sex-specific impacts of exercise, and have laid the ground work for more extensive studies of how genetics, sex, environment, and aging interact with exercise to influence metabolic fitness in Drosophila.
Highlights
Obesity is a health concern that has reached epidemic proportions and has been the subject of international legislation in an attempt to curb its prevalence [1]
The protocols we present here give two alternatives for a five-day exercise regime: one using short bouts separated by short rest times over approximately two hours daily with a gradual increase in bout duration over the week (Study A, S1 Table) and a second with a continuous two-hour bout of moderate induced exercise daily (Study B)
Controls either consisted of enclosures with restricted space for movement loaded on the TreadWheel (Fig 1C) or enclosures set immediately next to the TreadWheel to control for noise and vibrations
Summary
Obesity is a health concern that has reached epidemic proportions and has been the subject of international legislation in an attempt to curb its prevalence [1]. The leading hypothesis for the primary cause of the recent surge in obesity in the US is increases in both sedentary behavior and caloric intake [2]. Current treatment options for obesity include surgical interventions such as gastric bypass and lifestyle interventions such as weight-loss through changes in exercise and diet. Exercise induced weight-loss has almost no inherent risks and can be effective in reducing the severity of psoriasis [4], increasing insulin sensitivity [5], and acting as a preventative measure for conditions such as cardiovascular disease [6]. Regular exercise and moderate activity levels are considered important components of maintaining a healthy lifestyle [7]
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