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HERO ID
3350270
Reference Type
Journal Article
Title
Dibutyl Phthalate Exposure Disrupts Evolutionarily Conserved Insulin and Glucagon-Like Signaling in Drosophila Males
Author(s)
Williams, MJ; Wiemerslage, L; Gohel, P; Kheder, S; Kothegala, LV; Schioth, HB
Year
2016
Is Peer Reviewed?
Yes
Journal
Endocrinology
ISSN:
0013-7227
EISSN:
1945-7170
Volume
157
Issue
6
Page Numbers
2309-2321
Language
English
PMID
27100621
DOI
10.1210/en.2015-2006
Web of Science Id
WOS:000377214600012
Abstract
Phthalate diesters are commonly used as industrial plasticisers, as well as in cosmetics and skin care products, as a result people are constantly exposed to these xenobiotics. Recent epidemiological studies have found a correlation between circulating phthalate levels and type 2 diabetes, whereas animal studies indicate that phthalates are capable of disrupting endocrine signaling. Nonetheless, how phthalates interfere with metabolic function is still unclear. Here, we show that feeding Drosophila males the xenobiotic dibutyl phthalate (DBP) affects conserved insulin- and glucagon-like signaling. We report that raising flies on food containing DBP leads to starvation resistance, increased lipid storage, hyperglycemia, and hyperphagia. We go on to show that the starvation-resistance phenotype can be rescued by overexpression of the glucagon analogue adipokinetic hormone (Akh). Furthermore, although acute DBP exposure in adult flies is able to affect insulin levels, only chronic feeding influences Akh expression. We establish that raising flies on DBP-containing food or feeding adults DBP food affects the expression of homologous genes involved in xenobiotic and lipid metabolism (AHR [Drosophila ss], NR1I2 [Hr96], ABCB1 [MDR50], ABCC3 [MRP], and CYP3A4 [Cyp9f2]). Finally, we determined that the expression of these genes is also influenced by Akh. Our results provide comprehensive evidence that DBP can disrupt metabolism in Drosophila males, by regulating genes involved in glucose, lipid, and xenobiotic metabolism.
Keywords
ATP Binding Cassette Transporter, Subfamily B/metabolism; Animals; Cytochrome P-450 CYP3A/metabolism; Dibutyl Phthalate/toxicity; Drosophila; Drosophila Proteins/metabolism; Environmental Pollutants/toxicity; Glucagon/metabolism; Insulin/metabolism; Lipid Metabolism/drug effects; Signal Transduction/drug effects; Xenobiotics/metabolism; 2286E5R2KE; 9007-92-5
Tags
IRIS
•
Dibutyl Phthalate (DBP)
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Litsearch Jan 2016 - July 2016
Pubmed
WOS
LitSearch Jul 2016 - Jan 2017
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