Acetylator Genotype-Dependent Dyslipidemia in Rats Congenic for N-Acetyltransferase 2. (2020)

• Record Type: Journal Article
• Authors: Hong, Kyung U.; Doll, Mark A.; Lykoudi, Angeliki; Salazar-González, Raúl A.; Habil, Mariam R.; Walls, Kennedy M.; Bakr, Alaa F.; Ghare, Smita S.; Barve, Shirish S.; Arteel, Gavin E.; Hein, David W.
• Is Part Of: Toxicology reports. Volume 7(2020)
• Page Start: 1319
• Page End: 1330
• Publication Date: 2020
• Subjects: AUC area under the curve -- CD control diet -- GWAS genome-wide association study -- HFD high-fat diet -- invAUC inverse area under the curve -- ITT insulin tolerance test -- NAT arylamine N-acetyltransferase -- OGTT oral glucose tolerance test -- TC total cholesterol; Arylamine N-acetyltransferase -- obesity -- insulin resistance -- metabolic syndrome -- diet -- dyslipidemia; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2020.09.011
• Languages: English
• ISSNs: 2214-7500

Abstract

Graphical abstract: Highlights: Interactions between sex, diet & Nat2 were investigated in rats congenic for Nat2. Rapid Nat2 congenic rats developed greater dyslipidemia. Total cholesterol (TC)-to-HDL ratios were significantly higher in rapid Nat2 rats. HDL-to-LDL ratios were significantly lower in rapid Nat2 rats. Rapid Nat2 rats may have increased risk towards metabolic & cardiovascular disease. Abstract: Recent reports suggest that arylamine N -acetyltransferases (NAT1 and/or NAT2) serve important roles in regulation of energy utility and insulin sensitivity. We investigated the interaction between diet (control vs. high-fat diet) and acetylator phenotype (rapid vs. slow) using previously established congenic rat lines (in F344 background) that exhibit rapid or slow Nat2 (orthologous to human NAT1) acetylator genotypes. Male and female rats of each genotype were fed control or high-fat (Western-style) diet for 26 weeks. We then examined diet- and acetylator genotype-dependent changes in body and liver weights, systemic glucose tolerance, insulin sensitivity, and plasma lipid profile. Male and female rats on the high fat diet weighed approximately 10% more than rats on the control diet and the percentage liver to body weight was consistently higher in rapid than slow acetylator rats. Rapid acetylator rats were more prone to develop dyslipidemia overall (i.e., higher triglyceride; higher LDL; and lower HDL), compared to slow acetylator rats. Total cholesterol (TC)-to-HDL ratios were significantly higher and HDL-to-LDL ratios were significantly lower in rapid acetylator rats. Our data suggest that rats with rapid systemic Nat2 (NAT1 in humans) genotype exhibited higher dyslipidemia conferring risk for metabolic syndrome and cardiovascular dysfunction.