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The Effects of Postnatal Chlorpyrifos Exposure and Consumption of a Western Diet on Health.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Effects of Postnatal Chlorpyrifos Exposure and Consumption of a Western Diet on Health./
作者:	Yokoyama, Amy Shigeko.
面頁冊數:	1 online resource (125 pages)
附註:	Source: Dissertations Abstracts International, Volume: 79-06, Section: B.
Contained By:	Dissertations Abstracts International79-06B.
標題:	Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10623390click for full text (PQDT)
ISBN:	9780355451689

The Effects of Postnatal Chlorpyrifos Exposure and Consumption of a Western Diet on Health.
Yokoyama, Amy Shigeko.

The Effects of Postnatal Chlorpyrifos Exposure and Consumption of a Western Diet on Health. - 1 online resource (125 pages)

Source: Dissertations Abstracts International, Volume: 79-06, Section: B.

Thesis (Ph.D.)--University of California, Davis, 2017.

Includes bibliographical references

Despite its substantial societal and economic burden, the etiology of dementia remains elusive. Several studies have demonstrated that dementia is associated with consumption of a Western diet (WD; high fat, high sucrose, added cholesterol), yet the mechanisms behind this association are unknown. Recent research suggests that epigenetic alterations within the brain, particularly changes in DNA methylation, may be important in this regard. We hypothesized that consumption of a WD in male mice for three months alters DNA methylation in the brain and in doing so, contributes to dementia. Liver histological analysis coupled with analysis of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) revealed that mice fed a WD presented with increased liver lipidosis and hepatocyte injury compared with mice fed a control diet (CD). Moreover, we observed a significant decrease in global DNA methylation in the brains of WD-fed mice. We further identified several networks and pathways related to metabolism, cell adhesion and cytoskeleton integrity, inflammation and neurological function containing genes with significant differential methylation in mice fed a WD compared with mice fed a CD. In addition, the observations that 1) cognitive decline is associated with postnatal exposure to the organophosphate pesticide, chlorpyrifos (CPF) and 2) individuals with the greatest exposure to this pesticide often consume foods characteristic of a WD, prompted our desire to study the effects of both factors on phenotype and DNA methylation in male and female rats. Surprisingly, fasted serum levels of triglycerides and cholesterol were lower in both male and female rats fed a WD compared with those fed a CD. Based on histological analyses of the liver, we hypothesize that this is because rats fed a WD are more adept at shuttling lipid from the blood to the appropriate storage tissue, though there appears to be a sex-specific difference in the site of lipid storage. Both males and females displayed evidence of hepatocyte injury as determined by elevated levels of fasting serum ALT and AST. Interestingly, the only effect of CPF dose on any of the parameters studied was on fasting serum insulin; fasting serum insulin was significantly lower in male and female rats treated with 1 mg/kg CPF compared with those treated with vehicle or 3 mg/kg CPF. There were no significant changes in cortical gene expression of the neuroinflammatory-related genes Aif1, Gfap, Il1β and Il6, nor were there any significant changes in global DNA methylation. Together, our results suggest that postnatal exposure to CPF and consumption of a WD alter lipid and glucose metabolism, though their effect on DNA methylation and potentially dementia pathology is less clear.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9780355451689Subjects--Topical Terms:

530508
Genetics.
Subjects--Index Terms:

Alzheimer's diseaseIndex Terms--Genre/Form:

542853
Electronic books.

The Effects of Postnatal Chlorpyrifos Exposure and Consumption of a Western Diet on Health.
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520 $a Despite its substantial societal and economic burden, the etiology of dementia remains elusive. Several studies have demonstrated that dementia is associated with consumption of a Western diet (WD; high fat, high sucrose, added cholesterol), yet the mechanisms behind this association are unknown. Recent research suggests that epigenetic alterations within the brain, particularly changes in DNA methylation, may be important in this regard. We hypothesized that consumption of a WD in male mice for three months alters DNA methylation in the brain and in doing so, contributes to dementia. Liver histological analysis coupled with analysis of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) revealed that mice fed a WD presented with increased liver lipidosis and hepatocyte injury compared with mice fed a control diet (CD). Moreover, we observed a significant decrease in global DNA methylation in the brains of WD-fed mice. We further identified several networks and pathways related to metabolism, cell adhesion and cytoskeleton integrity, inflammation and neurological function containing genes with significant differential methylation in mice fed a WD compared with mice fed a CD. In addition, the observations that 1) cognitive decline is associated with postnatal exposure to the organophosphate pesticide, chlorpyrifos (CPF) and 2) individuals with the greatest exposure to this pesticide often consume foods characteristic of a WD, prompted our desire to study the effects of both factors on phenotype and DNA methylation in male and female rats. Surprisingly, fasted serum levels of triglycerides and cholesterol were lower in both male and female rats fed a WD compared with those fed a CD. Based on histological analyses of the liver, we hypothesize that this is because rats fed a WD are more adept at shuttling lipid from the blood to the appropriate storage tissue, though there appears to be a sex-specific difference in the site of lipid storage. Both males and females displayed evidence of hepatocyte injury as determined by elevated levels of fasting serum ALT and AST. Interestingly, the only effect of CPF dose on any of the parameters studied was on fasting serum insulin; fasting serum insulin was significantly lower in male and female rats treated with 1 mg/kg CPF compared with those treated with vehicle or 3 mg/kg CPF. There were no significant changes in cortical gene expression of the neuroinflammatory-related genes Aif1, Gfap, Il1β and Il6, nor were there any significant changes in global DNA methylation. Together, our results suggest that postnatal exposure to CPF and consumption of a WD alter lipid and glucose metabolism, though their effect on DNA methylation and potentially dementia pathology is less clear.
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538 $a Mode of access: World Wide Web
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650 4 $a Toxicology. $3 556884
650 4 $a Nutrition. $3 517777
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