Progress 10/01/17 to 09/30/18
Outputs
Target Audience:Our target audience is researchers, medical professionals, and individuals diagnosed with polycystic kidney disease(PKD).Previously, we published that rats with polycystic kidney disease fed diets supplemented with soy protein isolate and omega-3 polyunsaturated fatty acids had significantly increase liver lipid accumulation. In addition, we observed splenomegaly. Therefore, we investigated whether splenomagly may have contributed to the liver steatosis. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?M.S.student, LaurenGibson's thesisexpandedthis result byinvestigating potential mechanism for hepatic steatosis. Particularly, the involvement of the spleen-liver axis.Some aims were included in undergraduate project for Mitch Baranski, BABiology resulted in his co-authorship on a published conference abstract. Joining this project as collaborators were Dr. Vagner Benedito, Genetics and Development Biology, WVU and Dr. Ryan Livengood from Dept. of Pathology at United Hospital Center, WV. How have the results been disseminated to communities of interest?The results have been presented at local research symposiums, national, and international conferences and have been subsequently published in nutrition journals as original research as well as a review article. What do you plan to do during the next reporting period to accomplish the goals?We plan to publish the results of our findings investigating soy protein Isolate and/or omega-3 polyunsaturated fatty acids had no influences on the spleen-liver axis in a female rat model of autosomal recessive polycystic kidney disease with liver steatosis in a peer reviewed journal. After which this Hatch Project is completed.
Impacts
What was accomplished under these goals?
The most common extra-renal manifestation ofautosomal polycystickidney disease is liver disease with a greater rate in females due to their higher estrogen levels. Abnormal spleen enlargement (splenomegaly) has been found to occur in 60% ofautosomal recessive polycystic diseasepatients. In the absence of effective medications to treat the hepatic and splenic complications of ARPKD, diet offers a potentially efficacious, safe, and cost-effective therapy. Results showed at that soy protein isolate and omega-3 polyunsaturated fatty acids had no effect on splenomegaly and splenomegaly did not significantly contribute to the development of liver steatosis in a female PCK rat model. The thesis entitled "Feeding Soy Protein Isolate and/or Omega-3 Polyunsaturated Fatty Acids on the Spleen-Liver Axis in a Female Rat Model of Autosomal Recessive Polycystic Kidney Disease with Liver Steatosis" was submitted defended in May 2017. The publication was submitted in 2018 but rejected due to suggestions for more experiments. Biochemistry undergraduate student, Mitch Baranski conducted an additional experiement and the paper is now being analyzed and rewritten.
Publications
- Type:
Theses/Dissertations
Status:
Submitted
Year Published:
2017
Citation:
Biology Meeting in April 2016 at San Diego.
Gibson L. The effect of feeding soy protein isolate and/or omega-3 polyunsaturated fatty acids on the spleen-liver axis in a female PCK rat model of autosomal recessive polycystic kidney disease.
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Progress 01/10/14 to 09/30/18
Outputs
Target Audience:Our target audience is researchers, medical professionals, and individuals diagnosed with polycystic kidney disease(PKD).Previously, we published that rats with polycystic kidney disease fed diets supplemented with soy protein isolate and omega-3 polyunsaturated fatty acids had significantly increase liver lipid accumulation. In addition, we observed splenomegaly. Therefore, we investigated whether splenomagly may have contributed to the liver steatosis. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?All three aims were achieved by Kaitlin Maditz as partial fulfilment of her doctoral thesis. Aim II showed feeding young female PCK rats soy protein and n-3 PUFA failed to attenuate liver cyst progression. Furthermore, feeding soy protein and n-3 PUFA as fish oil resulted in complications of hepatic steatosis. M.S.student, LaurenGibson's thesisexpandedthis result byinvestigating potential mechanism for hepatic steatosis. Particularly, the involvement of the spleen-liver axis.Some aims were included in undergraduate project for Mitch Baranski, BABiology resulted in his co-authorship on a published conference abstract. Joining this project as collaborators were Dr. Vagner Benedito, Genetics and Development Biology, WVU and Dr. Ryan Livengood from Dept. of Pathology at United Hospital Center, WV. How have the results been disseminated to communities of interest?The university and public was invited to MS student Lauren Gibson seminar entitled "Soy Protein Isolate and/or Omega-3 Polyunsaturated Fatty Acids had no influences on the Spleen-Liver Axis in a Female Rat Model of Autosomal Recessive Polycystic Kidney Disease with Liver Steatosis"presented May 2016. What do you plan to do during the next reporting period to accomplish the goals?We plan to publish the results of our findings investigating soy protein Isolate and/or omega-3 polyunsaturated fatty acids had no influences on the spleen-liver axis in a female rat model of autosomal recessive polycystic kidney disease with liver steatosis in a peer reviewed journal. We plan to continue to investigated other extra-hepatic and co-morbidities associated with diet and autosomal recessive polycystic kidney disease. After which the project will close. A new Hatch project on Apple Pomace has been submitted and approved.
Impacts
What was accomplished under these goals?
The most common extra-renal manifestation ofautosomal polycystickidney disease is liver disease with a greater rate in females due to their higher estrogen levels. Abnormal spleen enlargement (splenomegaly) has been found to occur in 60% ofautosomal recessive polycystic diseasepatients. In the absence of effective medications to treat the hepatic and splenic complications of ARPKD, diet offers a potentially efficacious, safe, and cost-effective therapy. Results showed at that soy protein isolate and omega-3 polyunsaturated fatty acids had no effect on splenomegaly and splenomegaly did not significantly contribute to the development of liver steatosis in a female PCK rat model. The abstract entitled "Feeding Soy Protein Isolate and/or Omega-3 Polyunsaturated Fatty Acids on the Spleen-Liver Axis in a Female Rat Model of Autosomal Recessive Polycystic Kidney Disease with Liver Steatosis" was submitted and accepted forpresented at the Experimental Biology Meeting in April 2016 at San Diego. MS student Lauren Gibson completed her thesis entitled "Soy Protein Isolate and/or Omega-3 Polyunsaturated Fatty Acids had no influences on the Spleen-Liver Axis in a Female Rat Model of Autosomal Recessive Polycystic Kidney Disease with Liver Steatosis" in May 2016.
Publications
- Type:
Theses/Dissertations
Status:
Submitted
Year Published:
2017
Citation:
Gibson L. The effect of feeding soy protein isolate and/or omega-3 polyunsaturated fatty acids on the spleen-liver axis in a female PCK rat model of autosomal recessive polycystic kidney disease.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Gibson L, Maditz K, Benedito V, Tou JC. The Effects of Feeding Soy Protein Isolate and/or Omega-3 Polyunsaturated Fatty Acids on the Spleen of Female PCK Rats. FASEB J A915.35
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Progress 10/01/16 to 09/30/17
Outputs
Target Audience:Our target audience is researchers, medical professionals, and individuals diagnosed with polycystic kidney disease(PKD).Previously, we published that rats with polycystic kidney disease fed diets supplemented with soy protein isolate and omega-3 polyunsaturated fatty acids had significantly increase liver lipid accumulation. In addition, we observed splenomegaly. Therefore, we investigated whether splenomegaly may have contributed to the liver steatosis. The paper was submitted and is current in review. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?We plan to continue to investigate other extra-hepatic and co-morbidities associated with diet and autosomal recessive polycystic kidney disease. Currently, B.S. Biochemistry Thesis Honors student is investigating the effect of feeding soy protein (containing phytoestrogens) on uterus and ovaries since both are estrogen-sensitive organs. Joining this project as collaborators were Dr. Vagner Benedito, Genetics and Development Biology, WVU and Dr. Ryan Livengood from Dept. of Pathology at United Hospital Center, WV. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?We are currently preforming a histological evaluation of the ovaries and uterus. We are also performing microscope examinations of the vaginal lavages taken throughout the 12 weeks study to determine any estrous cycling changes. We plan to measure serum estradiol, progesterone, GnRH and leptin,
Impacts
What was accomplished under these goals?
The most common extra-renal manifestation ofautosomal polycystickidney disease is liver disease with a greater rate in females due to their higher estrogen levels. Abnormal spleen enlargement (splenomegaly) has been found to occur in 60% ofautosomal recessive polycystic diseasepatients. In the absence of effective medications to treat the hepatic and splenic complications of ARPKD, diet offers a potentially efficacious, safe, and cost-effective therapy. Results showed at that soy protein isolate and omega-3 polyunsaturated fatty acids had no effect on splenomegaly and splenomegaly did not significantly contribute to the development of liver steatosis in a female PCK rat model. The paper entitled "Feeding Soy Protein Isolate and/or Omega-3 Polyunsaturated Fatty Acids on the Spleen-Liver Axis in a Female Rat Model of Autosomal Recessive Polycystic Kidney Disease with Liver Steatosis" was submitted for publication to J Pediatr Gastroenterol Nutr. All three aims were achieved by Kaitlin Maditz as partial fulfilment of her doctoral thesis. Aim II showed feeding young female PCK rats soy protein and n-3 PUFA failed to attenuate liver cyst progression. Furthermore, feeding soy protein and n-3 PUFA as fish oil resulted in complications of hepatic steatosis. M.S.student, LaurenGibson's thesisexpandedthis result byinvestigating potential mechanism for hepatic steatosis. Particularly, the involvement of the spleen-liver axis.
Publications
- Type:
Journal Articles
Status:
Under Review
Year Published:
2017
Citation:
Gibson L, Maditz KM, Benedito V, Tou JC. The effect of feeding soy protein isolate and/or omega-3 polyunsaturated fatty acids on the spleen-liver axis in a female PCK rat model of autosomal recessive polycystic kidney disease disease.
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Progress 10/01/15 to 09/30/16
Outputs
Target Audience:Our target audience is researchers, medical professionals, and individuals diagnosed with polycystic kidney disease (PKD).Previously, we published that rats with polycystic kidney disease fed diets supplemented with soy protein isolate and omega-3 polyunsaturated fatty acids had signficantly increase liver lipid accumulation. In addition, we observed splenomegaly. Therefore, we investigated whether splenomagly may have contributed to the liver steatosis. The abstract was submitted and accepted forpresented at the Experimental Biology Meeting in April 2016 at San Diego. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?All three aims were achieved by Kaitlin Maditz as partial fulfilment of her doctoral thesis. Aim II showed feeding young female PCK rats soy protein and n-3 PUFA failed to attenuate liver cyst progression. Furthermore, feeding soy protein and n-3 PUFA as fish oil resulted in complications of hepatic steatosis. M.S.student, LaurenGibson's thesisexpandedthis result byinvestigating potential mechanism for hepatic steatosis. Particularly, the involvement of the spleen-liver axis.Some aims were included in undergraduate project for Mitch Baranski, BABiology resulted in his co-authorship on a published conference abstract. Joining this project as collaborators were Dr. Vagner Benedito, Genetics and Development Biology, WVU and Dr. Ryan Livengood from Dept. of Pathology at United Hospital Center, WV. How have the results been disseminated to communities of interest?The university and public was invited to MS student Lauren Gibson seminar entitled "Soy Protein Isolate and/or Omega-3 Polyunsaturated Fatty Acids had no influences on the Spleen-Liver Axis in a Female Rat Model of Autosomal Recessive Polycystic Kidney Disease with Liver Steatosis"presented May 2016. What do you plan to do during the next reporting period to accomplish the goals?We plan to publish the results of our findings investigating soy protein Isolate and/or omega-3 polyunsaturated fatty acids had no influences on the spleen-liver axis in a female rat model of autosomal recessive polycystic kidney disease with liver steatosis in a peer reviewed journal. We plan to continue to investigated other extra-hepatic and co-morbidities associated with diet and autosomal recessive polycystic kidney disease.
Impacts
What was accomplished under these goals?
The most common extra-renal manifestation ofautosomal polycystickidney disease is liver disease with a greater rate in females due to their higher estrogen levels. Abnormal spleen enlargement (splenomegaly) has been found to occur in 60% ofautosomal recessive polycystic diseasepatients. In the absence of effective medications to treat the hepatic and splenic complications of ARPKD, diet offers a potentially efficacious, safe, and cost-effective therapy. Results showed at that soy protein isolate and omega-3 polyunsaturated fatty acids had no effect on splenomegaly and splenomegaly did not significantly contribute to the development of liver steatosis in a female PCK rat model. The abstract entitled "Feeding Soy Protein Isolate and/or Omega-3 Polyunsaturated Fatty Acids on the Spleen-Liver Axis in a Female Rat Model of Autosomal Recessive Polycystic Kidney Disease with Liver Steatosis" was submitted and accepted forpresented at the Experimental Biology Meeting in April 2016 at San Diego. MS student Lauren Gibson completed her thesis entitled "Soy Protein Isolate and/or Omega-3 Polyunsaturated Fatty Acids had no influences on the Spleen-Liver Axis in a Female Rat Model of Autosomal Recessive Polycystic Kidney Disease with Liver Steatosis" in May 2016.
Publications
- Type:
Theses/Dissertations
Status:
Accepted
Year Published:
2016
Citation:
Gibson L. The effect of feeding soy protein isolate and/or omega-3 polyunsaturated fatty acids on the spleen-liver axis in a female PCK rat model of autosomal recessive polycystic kidney disease disease.
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Progress 10/01/14 to 09/30/15
Outputs
Target Audience:Our target audience is researchers, medical professionals, and individuals diagnosed with polycystic kidney disease (PKD) and their families. PKD an incurable inherited disease characterized by renal cysts and is a leading cause of end-stage renal disease. Dietary intervention offers a potentially efficacious, cost-effective, and safe therapeutic option for PKD and PKD-related complications. Cyst lesions in the liver should also been studied since it is a major cause of morbidity and mortality in autosomal recessive polycystic kidney disease patients who survive infancy. A better understanding of the role of bioactive nutrients in PKD can contribute to the development of dietary recommendations and diet-based therapies to reduce PKD progression, severity and related co-morbidities. Information regarding the role of dietary components obtained from animal models of PKD can benefit human PKD patients by providing a better understanding of pathways to target in order to inhibit cyst pathogenesis in the kidneys, liver, and extra-hepatic tissues. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?All 3 aims werecompleted by Kaitlin Maditz as partial fulfilment of her doctoral thesis.Supporting these aimswereundergraduate honor's thesescompleted byChris Oldaker, BA Biology and Nanika Nanda, B.S. Chemistrywhich alsoresulted in their co-authorship inour subsequent peer-reviewed publications.Measurement ofadditional gene markersof liverinflammation and fibrosis was the project for Summer Undergraduate Research Education (SURE) student, Sundus Lateef and measurement of additional serum bone markers was the project for SURE student Matthew Millerwhich resulted in their co-authorship inour subsequent peer-reviewed publications. Joining this project as collaborators were Drs. Brenda Smith from the Dept. of Nutritional Sciences at University of Oklahoma State, Ryan Livengood from Dept. Pathology at United Hospital Center, WV, and Dr. Vagner Benedito, Genetics and Developmental Biology, WVU. Currently, M.S. Student Lauren Gibson is investigating the spread of cysts in the spleen in PKD rats. How have the results been disseminated to communities of interest?The resultsof diet on bone and liver cysts were presented at internal research competitions and international conferences and have been subsequently published in medical and nutrition journals as an original research article as well as a review article. What do you plan to do during the next reporting period to accomplish the goals?We are currently investigating potential mechanisms responsible for the unexpected finding of liver steatosis in PKD rats fed a diet rich in soy protein and n-3 PUFA as fish oil. We are also investigating the spread of cysts to extra-hepatic tissues such as the spleen, brain, and reproductive tissues. This research is currently in progress.
Impacts
What was accomplished under these goals?
Although liver cysts is one of the most common co-morbidities accompanying PKD, to our knowledge no studies have investigated the effect of diet on hepatic cysts. Based on our study results, feeding soy protein and n-3 PUFA to young female PCK rats failed to attenuate liver cyst progression. Furthermore, feeding soy protein and n-3 PUFA as fish oil resulted as hepatic steatosis. Unexpectedly, results suggested our diet worsened liver complications associated with PKD. Bone health is also of particular concern since mineral metabolism and bone also worsens with progressive loss of kidney function. Optimizing bone health during the growth stage may preserve against bone loss associated with early renal dysfunction in PKD. Dietary soy protein and n-3 PUFA have been reported to ameliorate PKD and to promote bone health. Based on our results early diet management of PKD using soy protein and/or n-3 PUFAs influenced bone longitudinal growth and mineral balance, but neither worsened nor enhanced bone mineralization, microarchitecture or strength.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
Maditz KH, Smith BJ, Miller M, Oldaker C, Tou JC. Feeding soy protein isolate and oils rich in omega-3 polyunsaturated fatty acids affected mineral balance, but not bone in a rat model of autosomal recessive polycystic kidney disease. BMC Nephrol. 2015;10:16:13.
Maditz KH, Benedito VA, Oldaker C, Nanda N, Lateef SS, Livengood R, Tou JC. Feeding soy protein isolate and n-3 PUFA affects polycystic liver disease progression in a PCK rat model of autosomal polycystic kidney disease. J Pediatr Gastroenterol Nutr. 2015;60:467-73.
Tou JC, Maditz KH, Gigliotti JC. Evaluating the therapeutic value of omega-3 polyunsaturated fatty acid supplementation on polycystic kidney disease and co-morbidities. Curr Opin Food Sci. 2015;2: 20-28.
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Progress 01/10/14 to 09/30/14
Outputs
Target Audience: Our target audience is researchers, medical professionals, and individuals diagnosed with polycystic kidney disease (PKD) and their families. PKD an incurable inherited disease characterized by renal cysts and is a leading cause of end-stage renal disease. Dietary intervention offers a potentially efficacious, cost-effective, and safe therapeutic option for PKD and PKD-related complications. Cyst lesions in the liver should also been studied since it is a major cause of morbidity and mortality in autosomal recessive polycystic kidney disease patients who survive infancy. A better understanding of the role of bioactive nutrients in PKD can contribute to the development of dietary recommendations and diet-based therapies to reduce PKD progression, severity and related co-morbidities. Information regarding the role of dietary components obtained from animal models of PKD can benefit human PKD patients by providing a better understanding of pathways to target in order to inhibit cyst pathogenesis in the kidneys and liver. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? Freshman chemistry Sundus Lateef’s Summer Undergraduate Research Education (SURE) project entitled “Why do omega-3 fatty acids and soy protein promote fatty liver in polycystic liver disease” that won 3rd place in the SURE research competition. Sundus is now pursuing an honor research project on diet a polycystic liver disease. Doctoral student Kaitlin Maditz presented her research dietary n-3 polyunsaturated fatty acids or soy protein isolate did not attenuate disease progression in a female rat model of autosomal recessive polycystic kidney disease at Experimental Biology and Medicine in San Diego, April 2014. How have the results been disseminated to communities of interest? The results have presented atinternal research competitions andinternational conferences and have been subsequentlypublished in medical and nutrition journals as an original research article and review article.The Maditz et al. publication on diet therapy and PKD is in Nutrition Review which is ranked as 7th in the Nutrition and Dietetics field and was voted by physicians as the #1 article in nephrology in MDLink. What do you plan to do during the next reporting period to accomplish the goals? We arecurrently investigating the role of n-3 PUFAs on polycystic liver disease progression and severity in PKD. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist has been reported to be effective at reducing hepatic cystic lesions and fibrosis in an animal model. The n-3 PUFAs are a natural ligand for PPARγ and therefore, may attenuate liver cyst severity. Female PCK rats (n=12/group) were fed diets consisting of casein + corn oil (Casein + CO), casein + soybean oil (Casein + SO), SPI + soybean oil (SPI + SO) or SPI + 1:1 soybean/salmon oil (SPI + B) for 12-weeks. The researchis in progress.
Impacts
What was accomplished under these goals?
PKD is a leading cause of end stage renal failure, resulting in the need for transplantation or long-term dialysis. Animal studies have advanced existing knowledge of PKD and potential therapeutic treatments. Inflammation is a common pathology in disease progression and severity. Soy protein isolate (SPI) and omega-3 fatty acids (n-3 PUFA’s) have been shown to have anti-inflammatory properties. Regardless of the protein source (i.e. soy protein versus casein) rats fed diets consisting of n-3 PUFA as soybean oil or 1:1 soybean oil and fish oil blend had higher renal n-3 PUFA content compared to rats fed corn oil. Real time quantitative polymerase chain reaction showed no differences in relative genetic expression of inflammation among the diet groups. Histological evaluation also showed no differences in renal interstitial inflammation. Based on the results, SPI and/or n-3 PUFAs did not appear to attenuate PKD severity by reducing inflammation.
Publications
- Type:
Journal Articles
Status:
Accepted
Year Published:
2014
Citation:
Maditz KH, Oldaker C, Nanda N, Benedito VA, Livengood R, Tou JC. Dietary n-3 polyunsaturated fatty acids or soy protein isolate did not attenuate disease progression in a female rat model of autosomal recessive polycystic kidney disease. Nutr Res (2014) 34:526-534.
- Type:
Journal Articles
Status:
Accepted
Year Published:
2014
Citation:
Tou JC, Gigliotti JC, Maditz KM. Evaluating the therapeutic value of omega-3 Polyunsaturated fatty acid supplementation on polycystic kidney disease and co-morbidities. Current Opinions in Food Science (accepted with revisions).
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