High fat diet-induced TGF-β/Gbb signaling provokes insulin resistance through the tribbles expression

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Title
High fat diet-induced TGF-β/Gbb signaling provokes insulin resistance through the tribbles expression
Author(s)
Seung Hyun Hong; Moonyoung Kang; Kyu-Sun LeeKweon Yu
Bibliographic Citation
Scientific Reports, vol. 6, pp. 30265-30265
Publication Year
2016
Abstract
Hyperglycemia, hyperlipidemia, and insulin resistance are hallmarks of obesity-induced type 2 diabetes, which is often caused by a high-fat diet (HFD). However, the molecular mechanisms underlying HFD-induced insulin resistance have not been elucidated in detail. In this study, we established a Drosophila model to investigate the molecular mechanisms of HFD-induced diabetes. HFD model flies recapitulate mammalian diabetic phenotypes including elevated triglyceride and circulating glucose levels, as well as insulin resistance. Expression of glass bottom boat (gbb), a Drosophila homolog of mammalian transforming growth factor-β (TGF-β), is elevated under HFD conditions. Furthermore, overexpression of gbb in the fat body produced obese and insulin-resistant phenotypes similar to those of HFD-fed flies, whereas inhibition of Gbb signaling significantly ameliorated HFD-induced metabolic phenotypes. We also discovered that tribbles, a negative regulator of AKT, is a target gene of Gbb signaling in the fat body. Overexpression of tribbles in flies in the fat body phenocopied the metabolic defects associated with HFD conditions or Gbb overexpression, whereas tribbles knockdown rescued these metabolic phenotypes. These results indicate that HFD-induced TGF-β/Gbb signaling provokes insulin resistance by increasing tribbles expression.
ISSN
2045-2322
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/srep30265
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > 1. Journal Articles
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