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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Food Science

Year Degree Awarded

2017

Month Degree Awarded

May

First Advisor

Yeonhwa Park

Second Advisor

John M. Clark

Third Advisor

Lili He

Fourth Advisor

David Julian McClements

Subject Categories

Environmental Health | Food Science | Toxicology

Abstract

Over the last few decades, the decline of using organochlorine and organophosphorus insecticides has partially contributed to the rising utilization of newer synthetic insecticides, which are considered as less harmful and more environmental friendly than the older generation of insecticides. Pyrethroid insecticides are one of the newer insecticide classes reported with better biodegradability and low mammalian toxicity without sacrificing its insecticidal efficacy. Permethrin is one of the most widely used pyrethroid insecticides with structural similarity with natural pyrethrin insecticide from the flowers of Chrysanthemum cinerariifolium. Since its introduction in the 1970’s, permethrin has been extensively used in medicine, military, household, industry and agriculture. Although a large body of evidence have supported that exposure to organochlorine and organophosphorus insecticides could increase the risk of developing obesity and diabetes, less attention has been drawn to pyrethroids. It has been reported recently that permethrin potentiated adipogenesis and insulin resistance in vitro. This study is designed to determine the effects of exposure to permethrin, along with the interaction with high-fat diet, on glucose and lipid metabolism in vivo. Our results demonstrated that chronic exposure to low level of permethrin could disturb glucose and lipid metabolisms in female and male mice in a diet-dependent manner. Exposure to permethrin significantly increased insulin resistance in male and female mice fed high-fat diet as demonstrated by impaired insulin sensitivity, glucose tolerance and increased HOMA-IR. Permethrin treatment also significantly increased weight gain and adipose tissue weight in high-fat fed male mice but not female mice. Further mechanistic studies in mice showed that permethrin can target AMPK pathway, AKT pathway, and fatty acid oxidation to influence glucose and lipid metabolisms. In vivo studies in 3T3-L1 adipocytes showed that permethrin potentiated adipogenesis via calcium- and endoplasmic reticulum (ER) stress- mediated mechanisms. The current results suggest that exposure to permethrin can potentially disturb glucose and lipid metabolisms resulting in increased risk of developing obesity and type 2 diabetes.

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