A high-sugar diet produces obesity and insulin resistance in wild-typeDrosophila

Abstract

SUMMARYInsulin-resistant, ‘type 2’ diabetes (T2D) results from a complex interplay between genes and environment. In particular, both caloric excess and obesity are strongly associated with T2D across many genetic backgrounds. To gain insights into how dietary excess affects insulin resistance, we studied the simple model organism Drosophila melanogaster. Larvae reared on a high-sugar diet were hyperglycemic, insulin resistant and accumulated fat – hallmarks of T2D – compared with those reared on control diets. Excess dietary sugars, but not fats or proteins, elicited insulin-resistant phenotypes. Expression of genes involved in lipogenesis, gluconeogenesis and β-oxidation was upregulated in high-sugar-fed larvae, as were FOXO targets, consistent with known mechanisms of insulin resistance in humans. These data establish a novel Drosophila model of diet-induced insulin resistance that bears strong similarity to the pathophysiology of T2D in humans.

Attenuation of high sucrose diet–induced insulin resistance in tryptophan 2,3-dioxygenase deficient Drosophila melanogaster vermilion mutants

“…Present data indicate that HSD delays pupae emergence from larva and imago eclosion in wild type C-S flies in according with literature data [11–13]. The main finding of the present study is that HSD-induced delay of pre-imaginal development (from egg through larva and pupa to imago) was two times shorter in white (C-S) mutants than in wild type C-S flies.…”

“…We are not aware of studies of the effect of HSD on preimaginal stages of ABC transporter deficient white flies. Considering that HSD-induced delay of pre-imaginal development is caused by IR [11–13], our data suggest that mutation of white gene attenuates HSD-induced IR.…”

“…Dysregulation of Trp-Kyn pathway in obesity was suggested [3,6] and supported by clinical and experimental data [27–29]. It is noteworthy that in Drosophila HSD induces not only IR/T2D but obesity as well [11]. Future studies of HSD-induced obesity in white mutants might provide better understanding of the role of Trp–Kyn pathway in mechanisms of obesity and T2D.…”

“…We found IR correlation with activity of Trp-Kyn pathway in Hepatitis C virus (HCV) patients [9], and elevation of plasma concentrations of Kyn downstream metabolites in T2D patients [10]. Experimental model of T2D was established in Drosophila melanogaster [11]. There are four distinct stages in the life of flies : egg, larva, pupa, and imago (adult).…”

Methods for studying metabolism in Drosophila

“…These diets consist of either 1% agar, 3.4% yeast, 8.3% cornmeal, and 30% sucrose [15] or 1% agar, 8% yeast, 2% yeast extract, 2% peptone, and 34.2% sucrose [18] (Table 1). These diets lead to hallmarks of type 2 diabetes in wild-type Drosophila , including hyperglycemia, insulin resistance, obesity, and cardiac dysfunction [15, 18, 19]. High lipid diets have also been developed for studies of diet-induced obesity in Drosophila .…”