Lauren Gibson

Date of Graduation

2016

Document Type

Thesis

Degree Type

MS

College

Davis College of Agriculture, Natural Resources and Design

Department

Animal and Nutritional Sciences

Committee Chair

Janet C Tou

Committee Co-Chair

Vagner A Benedito

Committee Member

Joseph S Moritz

Abstract

ABSTRACT 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 Lauren Brooke Gibson Autosomal recessive polycystic kidney disease (ARPKD) is a congenital hepatorenal fibrocystic syndrome with a mortality rate of 30% during the first year of life. The most common extra-renal manifestation of ARPKD 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% of ARPKD patients. 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 option. Soy protein isolate (SPI) has been shown to reduce cyst proliferation associated with its anti-estrogenic and anti-inflammatory actions. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects and influence mediators of de novo lipogenesis (DNL) through up-regulation of beta-oxidation. Young (age 28 days) female PCK rats, an orthologous animal model of ARPKD, were randomly assigned to one of four diets (n=12/group) and fed for 12 weeks. Diet groups consisted of 1) casein + corn oil (Casein + CO), 2) casein + soybean oil (Casein + SO), 3) soy protein isolate + soybean oil (SPI + SO), or 4) soy protein isolate + a 1:1 soybean: salmon oil blend (SPI + SB) rich in long chain n-3 PUFAs. Unexpectedly, SPI + SB fed rats had the highest histological evidence of hepatic steatosis (p=0.003) suggesting non-alcoholic fatty liver disease (NAFLD). NAFLD is the leading cause of chronic liver disease in adults and children consuming Westernized diets. The SPI + SB group also had increased (p=0.03) inflammation and up-regulated (p=0.03) expression of fibrosis related genes suggesting progression of NAFLD to non-alcoholic steatohepatitis (NASH). The spleen was also significantly (P=0.02) elongated in the SPI+SB fed group compared to the Casein + CO and Casein + SO groups. However, spleen weight was not significantly different among diet. We hypothesize the spleen-liver axis is responsible for the development of steatosis and fibrosis in our rats. Given the close anatomical proximity of the spleen to the liver bioactive compounds produced by the spleen such as splenic fatty acids, inflammatory and immune genes can directly access the liver via the splenic and portal veins. The objective of this study was to determine the effect of SPI and/or n-3 PUFAs on splenic DNL, lipolysis, inflammatory response, and immune gene expression. Results of DNL gene expression and splenic fatty acid content of DNL fatty acids were not significantly different among diet groups. Rats fed the SPI+SB diet containing the highest (P<0.001) dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibited the highest (P<0.001) splenic EPA and DHA, and the lowest (P=0.03) splenic arachidonic acid (AA) showing diet did effect the spleen with potentially anti-inflammatory effects. However, no significant differences in gene expression regulating inflammation or immunity were found among dietary treatment groups. Based on our results we concluded that diet had no effect on splenomegaly and splenomegaly did not significantly contribute to the development of liver steatosis in a female PCK rat model.

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