Date of Award

January 2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Animal Science

First Advisor

Shawn S Donkin

Committee Member 1

Kola Ajuwon

Committee Member 2

Shihuan Kuang

Committee Member 3

Dorothy Teegarden

Abstract

Pyruvate carboxylase (PC; EC 6.4.1.1) ostensibly links carbohydrate and lipid metabolism by supplying oxaloacetate (OAA) from the carboxylation of pyruvate. The OAA pool is necessary in maintaining the anaplerotic supply of carbons to the TCA cycle, and to promote the complete oxidation, to CO2, of acetyl-CoA. The actions of PC in supplying OAA are critical during periods of increased cellular lipid load, including the negative energy balance experienced by periparturient dairy cows. The bovine PC gene contains three promoter sequences, with products of the proximal promoter (PCP1) being specific to glucogenic and lipogenic tissues. Previous work links control of bovine PC mRNA expression to nonesterified fatty acids (NEFA), but the direct effects of saturated and unsaturated fatty acids on PC mRNA expression and subsequent fatty acid metabolism were unclear. The central hypothesis of this dissertation is that the ratio of the most prevalent circulating saturated and unsaturated fatty acids in dairy cows regulates PC flux and subsequent fatty acid metabolism. The objectives of this dissertation were, first, to evaluate the response of PC mRNA to the copresence of the most abundant circulating saturated and unsaturated fatty acids in periparturient dairy cows. Second, to determine the direct effects of these saturated and unsaturated fatty acids, and their combinations, on the cellular oxidation of fatty acids, and the potential relationship to PC, and third, to examine the effects of the copresence of saturated and unsaturated fatty acids on the transcriptional activity of bovine PCP1.

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