Date of Award

Summer 8-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Daniel Widzowski, Ph.D.

Second Advisor

Christina Ruby, Ph.D.

Third Advisor

Megan Knoch, Ph.D.

Abstract

It was hypothesized that olanzapine-induced weight gain could be related to both diet and thyroid hormone (T4) depletion due to olanzapine’s potent histamine-1 receptor (H1R) antagonism. Adolescent female C57Bl/6j mice were divided into groups for diets deriving 10, 30, 45, and 60% of their calories from fat. Each of these groups was then divided into a saline vehicle b.i.d, olanzapine 1 mg/kg b.i.d., and olanzapine 2 mg/kg b.i.d. group. Triprolidine, a potent selective H1R antagonist, was given to a separate group of mice at 5 mg/kg q.d. receiving a 10% fat diet as a mechanistic control. Propylthiouracil (PTU), an antithyroid drug, was given to another 10% fat group at 10 mg/kg q.d. as a positive control for T4 depletion. Food was given ad libidum and weighed weekly to determine weekly consumption. Blood samples (100 μL) were taken at baseline and day 29. Serum total T4 was determined by ELISA. Mice were sacrificed on day 30 and had the retroperitoneal and perirenal fat pads removed and weighed. Each group began with 8 mice. The 10% fat and 60% fat groups showed no significant difference in weight gain between vehicle and olanzapine groups. The 30% and 45% fat showed olanzapine induced weight gain in the 2 mg/kg b.i.d and both 1 and 2 mg/kg b.i.d respectively. The triprolidine group surprisingly showed robust weight gain as well on the 10% fat diet. All mice ate less by the final week of the study and most decreased weekly. Fat pad mass had no correlation with the olanzapine dose. However the vehicle mice receiving the 60% fat diet had significantly larger fat pads than those on 10% fat chow. There was no correlation found between any variables and T4 levels. The positive control (PTU) failed to reduce T4 as anticipated. The results relating dietary fat to olanzapine-induced weight gain can be used in the future to make dietary recommendations to patients and the systematic study will serve as a base for further olanzapine/diet studies. Triprolidine will be further investigated to relate higher fat diets to the weight gain shown with 10% calories from fat.

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