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Exposure to permethrin promotes high fat diet-induced weight gain and insulin resistance in male C57BL/6J mice.

ABSTRACT: Permethrin is a pyrethroid pesticide that was previously reported to promote fat accumulation and insulin resistance in vitro. A recent study in female mice also found that permethrin could promote high fat-induced insulin resistance. The effects of permethrin on glucose and lipid metabolisms in male mice, however, remain unknown. The purpose of this study was to investigate the effects and interactions of permethrin exposure (50, 500, and 5000 ?g/kg body weight/day) and dietary fat (low fat, 4% w/w; high fat, 20% w/w) on development of obesity and insulin resistance in male C57BL/6J mice. Our results showed that permethrin treatment significantly increased body weight, fat mass, and insulin resistance with high fat diet, but not with low fat diet, without influencing energy intake. Permethrin treatment also significantly increased serum levels of insulin, glucose, leptin, triglycerides and cholesterol. Further results showed that permethrin inhibited AMP-activated protein kinase in white adipose tissue. These results suggest that permethrin interacts with dietary fat to alter lipid and glucose metabolisms in male C57BL/6J mice.

SUBMITTER: Xiao X

PROVIDER: S-EPMC5756676 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Exposure to permethrin promotes high fat diet-induced weight gain and insulin resistance in male C57BL/6J mice.

Xiao Xiao X Sun Quancai Q Kim Yoo Y Yang Szu-Hao SH Qi Weipeng W Kim Daeyoung D Yoon Kyong Sup KS Clark John M JM Park Yeonhwa Y

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 20171123

Permethrin is a pyrethroid pesticide that was previously reported to promote fat accumulation and insulin resistance in vitro. A recent study in female mice also found that permethrin could promote high fat-induced insulin resistance. The effects of permethrin on glucose and lipid metabolisms in male mice, however, remain unknown. The purpose of this study was to investigate the effects and interactions of permethrin exposure (50, 500, and 5000 μg/kg body weight/day) and dietary fat (low fat, 4% ...[more]

PMID: 29175578

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Project description:BackgroundTo date, there is only scare evidence characterizing the temporal features and progression of metabolic dysfunction in high-fat diet (HFD)-fed obese mice. Hence, its specific pathogenesis remains unclear.MethodsSixty 6-week-old male C57BL/6J mice were randomly divided into HFD and control diet (CD) groups and sacrificed at 1, 5, 9, 13, 17, and 21 weeks, respectively. At weekly intervals, intraperitoneal glucose tolerance testing (IPGTT) and intraperitoneal insulin tolerance testing (IPITT) were performed in both groups. A detailed time course in HFD-fed mice was investigated by evaluating the initiation of glucose homeostasis impairment, dyslipidemia, systemic insulin sensitivity, monocyte chemoattractant protein-1 (MCP-1) levels, epididymal white adipose tissue (eWAT) expansion, macrophage content changes, pro-inflammatory (M1)/anti-inflammatory (M2) macrophage imbalance, lipid accumulation in the liver, and β-cell morphometry in the pancreas.ResultsIn the HFD group, progressive weight gain and impairments in glucose metabolism (elevated fasting blood glucose and area under the curve (AUC) of IPGTT) were observed from the 3rd week, and a significantly elevated AUC of IPITT was first detected after week 7 of HFD feeding. As for dyslipidemia, after 9 weeks of feeding, the low-density lipoprotein cholesterol level and total cholesterol level in HFD group were significantly higher than those in the CD group (all P < 0.05), whereas no significant differences were shown in triglyceride level. Adipocyte size increased significantly in the HFD group in the 1st week, a phenotypic switch in eWAT from anti-inflammatory (M2) to pro-inflammatory (M1) macrophages was observed in the 5th week, and the metabolic inflammation was distinct in eWAT in the 9th week. Additionally, liver steatosis was considerably obvious at the 17th week and pancreatic β-cell morphometry did not change during 21 weeks of HFD feeding.ConclusionThe eWAT expansion was detected early in HFD-induced obese mice, which occurred prior to obvious insulin resistance.

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Exposure to permethrin promotes high fat diet-induced weight gain and insulin resistance in male C57BL/6J mice.

Publications

Exposure to permethrin promotes high fat diet-induced weight gain and insulin resistance in male C57BL/6J mice.

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