Date of Award

January 2021

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical Sciences

First Advisor

Eric J. Murphy

Abstract

Although studies in animal and cell culture systems have demonstrated the importance of liver fatty acid-binding protein (FABP1) in liver lipid metabolism, the impact of Fabp1 gene ablation on brain fatty acid uptake and lipid metabolism in intact animals is unknown. To address this, we assessed the effect of Fabp1 gene ablation on uptake and esterification of [1-14C]20:4n-6 into liver and brain lipids in vivo using a steady-state kinetic model. Plasma radioactivity was increased in Fabp1 gene-ablated mice, suggesting that loss of FABP1 impairs hepatic uptake of 20:4n-6. Indeed, liver uptake of [1-14C]20:4n-6 into aqueous and organic fractions was reduced. 20:4n-6 metabolism and lipid composition were altered in both liver and brain tissue of Fabp1 gene-ablated mice. Importantly, phosphatidylinositol (PtdIns) mass was increased in both tissues. These results demonstrate that FABP1 is important in liver lipid metabolism and peripherally modulates brain fatty acid uptake and steady-state lipid levels.

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