Oxylipin profiles in an orthologous mouse model of autosomal dominant polycystic kidney disease
| dc.contributor.author | Koohgoli, Roxanna Yasmin | |
| dc.contributor.examiningcommittee | Suh, Miyoung (Food and Human Nutritional Sciences) | en_US |
| dc.contributor.examiningcommittee | Wigle, Jeffrey (Biochemistry and Medical Genetics) | en_US |
| dc.contributor.supervisor | Aukema, Harold (Food and Human Nutritional Sciences) | en_US |
| dc.date.accessioned | 2020-02-10T20:36:35Z | |
| dc.date.available | 2020-02-10T20:36:35Z | |
| dc.date.copyright | 2020-02-10 | |
| dc.date.issued | 2020 | en_US |
| dc.date.submitted | 2020-02-04T16:06:33Z | en_US |
| dc.date.submitted | 2020-02-10T17:56:33Z | en_US |
| dc.degree.discipline | Food and Human Nutritional Sciences | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of renal cysts, which ultimately causes renal failure. Previous studies have suggested that whole flaxseed or flax oil can slow disease progression. The first analysis in this thesis examined the effect of a flax protein isolate (FPI) on disease progression in an orthologous ADPKD2 model (Pkd2WS25/- mice). Male and female mice were provided diets containing FPI or casein protein for 13 weeks. Heart, kidney, liver, and serum were then taken. There were no differences in kidney weight or water content between groups, indicating that there was no difference in the effect of FPI compared to casein on disease progression in this model. Oxylipins are bioactive lipids that are formed from polyunsaturated fatty acids (PUFAs) and have proliferative and inflammatory properties, which are key elements of the pathogenesis of ADPKD. Altered levels of kidney oxylipins, liver cysts and heart abnormalities can occur in ADPKD. Serum oxylipins may provide a useful biomarker for disease, so in the second analysis of this thesis the oxylipin profiles in serum, heart, kidney, and livers of healthy and diseased mice that were provided the control diet in the first analysus were analyzed. Cytochrome P450 derived oxylipins in serum were reduced in the diseased animals, while lipoxygenase derived oxylipins were largely lower in the diseased heart and kidney, with no consistent pattern of differences in liver oxylipins observed. Little is known about sex effects on tissue oxylipin profiles, so in the third analysis of this thesis, sex differences in oxylipins from healthy male and female mice given the standard diet were examined. Serum oxylipins were generally higher in females, while heart and liver oxylipins were generally higher in males. In kidneys, cyclooxygenase derived oxylipins were generally higher in females, while oxylipins derived from other pathways were higher in males. These studies demonstrate that FPI and casein have similar effects on ADPKD disease progression. In addition, tissue oxylipins are uniquely altered by disease and sex, and the serum oxylipin profile has potential as a biomarker of disease progression in ADPKD. | en_US |
| dc.description.note | May 2020 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/34540 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Autosomal dominant polycystic kidney disease | en_US |
| dc.subject | Oxylipins | en_US |
| dc.subject | Flaxseed | en_US |
| dc.subject | Sex effects | en_US |
| dc.subject | Healthy vs disease oxylipins | en_US |
| dc.title | Oxylipin profiles in an orthologous mouse model of autosomal dominant polycystic kidney disease | en_US |
| dc.type | master thesis | en_US |