Date on Master's Thesis/Doctoral Dissertation

5-2021

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Hein, David

Committee Co-Chair (if applicable)

Hong, Kyung

Committee Member

Hong, Kyung

Committee Member

Conklin, Daniel

Committee Member

Hill, Bradford

Committee Member

Hood, Joshua

Author's Keywords

NAT2; HCA; metabolic syndrome

Abstract

Heterocyclic amines (HCAs) are formed when cooking meats at high temperatures or for long periods of time, and their major metabolic pathway includes hepatic N‑hydroxylation by CYP1A2 followed by O-acetylation by N-acetyltransferase 2 (NAT2). NAT2 is a highly polymorphic gene involved in metabolism of drugs and xenobiotics, and its single nucleotide polymorphisms (SNPs) produce phenotypes characterized as slow, intermediate, or rapid acetylator. Recent studies have documented associations between HCAs and insulin resistance and between certain NAT2 phenotypes and insulin resistance. In this study, we demonstrated that NAT2 activity and exposure to certain HCAs may alter cellular glucose and lipid homeostasis. Additionally, these results demonstrate changes in sensitivity to insulin following exposure to some HCAs. These findings are significant because they indicate a genetic component (NAT2 polymorphism) and an environmental component (dietary HCA exposure via consumption of cooked meat) in the pathogenesis of insulin resistance in hepatocytes of human origin.

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