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

Laura Palanker Musselman, Jill L. Fink, Kirk Narzinski, Prasanna Venkatesh Ramachandran, Sumitha Sukumar Hathiramani, Ross L. Cagan, Thomas J. Baranski

Research output: Contribution to journalArticle

227 Scopus citations

Abstract

Insulin-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.

Original languageEnglish (US)
Pages (from-to)842-849
Number of pages8
JournalDMM Disease Models and Mechanisms
Volume4
Issue number6
DOIs
StatePublished - Nov 2011

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Musselman, L. P., Fink, J. L., Narzinski, K., Ramachandran, P. V., Hathiramani, S. S., Cagan, R. L., & Baranski, T. J. (2011). A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila. DMM Disease Models and Mechanisms, 4(6), 842-849. https://doi.org/10.1242/dmm.007948