Obesity and nutrient sensing TOR pathway in flies and vertebrates: Functional conservation of genetic mechanisms

Abstract

The global prevalence of obesity has grown to epidemic proportions, and 400 million people are now considered to be obese. Excessive accumulation of dietary lipids (obesity) is a known risk factor for the development of deleterious metabolic conditions and has been strongly linked to the progression of heart disease and type 2 diabetes. Investigating the origin and effects of high-fat diet (HFD)-induced obesity and its genetic mediators is an important step in understanding the mechanisms that contribute to obesity. However, the mechanisms that underlie HFD pathophysiology have yet to be elucidated fully. Here we describe recent work in a Drosophila model to investigate the origin and genetic mechanisms that could underlie HFD-induced obesity, type 2 diabetes and cardiac dysfunction.

Figure 1

Simplified model of nutrient signaling pathways influencing metabolic responses. InR and TOR pathway components are virtually all unique orthologous genes in Drosophila. TOR signaling also receives inputs from the energy sensing AMPK. Future studies will elucidate how the components of the InR-TOR signaling pathway modulate fat accumulation due to high levels of dietary fats, using the versatility and genetic simplicity of the Drosophila model. Unlike the complexity and interrelation between these pathways in mammals, Drosophila is ideal to study their role in controlling complex traits like HFD effects on disease.