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Sex differences in response to chronic Angiotensin-(1-7) treatment in obesity

Author
White, Melissa
Published
[University Park, Pennsylvania] : Pennsylvania State University, 2019.
Physical Description
1 electronic document
Additional Creators
Arnold, Amy Christine
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Open Access.
Summary
Angiotensin (Ang)-(1-7) is a hormone of the vasodilatory arm of the renin-angiotensin system (RAS) known to play a positive role in regulation of blood pressure and glucose homeostasis. Previous studies have shown that in high fat diet (HFD)-induced obese male mice, circulating Ang-(1-7) levels are reduced and chronic restoration of this hormone reverses diet-induced insulin resistance; however, this has yet to be examined in female mice. We hypothesized that Ang-(1-7) would improve insulin sensitivity and glucose tolerance in obese female mice, to a similar extent as previous observations in obese male mice. To test this hypothesis, 5-week old male and female C57BL/6J mice were randomly placed on either a control diet (18% kcal from fat) or HFD (60% kcal from fat) for 11 weeks. After 8 weeks of designated diet, mice were implanted with an osmotic pump for chronic 3-week subcutaneous delivery of Ang-(1-7) [400ng/kg/min] or saline. During the last week of treatment, body composition was measured and intraperitoneal insulin and glucose tolerance tests were performed to assess insulin sensitivity and glucose tolerance, respectively. The study was concluded with body weight measurement followed by euthanasia and blood collection. There were similar increases in body mass and adiposity between sexes in response to HFD. Ang-(1-7) treatment produced minor but significant decreases in body weight and adiposity in both obese male and female mice, while increasing lean mass in only females. While both sexes tended to develop mild hyperglycemia in response to HFD, female mice developed less marked hyperinsulinemia. There was no effect of Ang-(1-7) on fasting glucose or insulin levels in any of the study groups. Male and female mice developed insulin resistance and glucose intolerance to a similar extent in response to HFD feeding. Ang-(1-7) improved insulin sensitivity in both sexes, but corrected glucose intolerance only in the obese female mice. There were no effects of sex or Ang-(1-7) treatment on any of the study outcomes in control diet fed mice. These collective data provide new evidence for sex differences in response to chronic Ang-(1-7) therapy in C57BL/6J mice. These findings further our understanding of sex-dependent RAS and obesity differences, and may have broader implications to inform on future therapeutics targeting Ang-(1-7) in a clinical setting.
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Dissertation Note
M.S. Pennsylvania State University 2019.
Technical Details
The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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