A readout of metabolic efficiency in arylamine N‐acetyltransferase‐deficient mice reveals minor energy metabolism changes

Abstract

Recent studies have revealed a possible link between the activities of polymorphic arylamine N‐acetyltransferases (NATs) and energy metabolism. We used a Nat1/Nat2 double knockout (KO) mouse model to demonstrate that ablation of the two Nat genes is associated with modest, intermittent alterations in respiratory exchange rate. Pyruvate tolerance tests show that double KO mice have attenuated hepatic gluconeogenesis when maintained on a high‐fat/high‐sucrose diet. Absence of the two Nat genes also leads to an increase in the hepatic concentration of coenzyme A in mice fed a high‐fat/high‐sucrose diet. Our results suggest a modest involvement of NAT in energy metabolism in mice, which is consistent with the absence of major phenotypic deregulation of energy metabolism in slow human acetylators.

The Arylamine N-Acetyltransferases as Therapeutic Targets in Metabolic Diseases Associated with Mitochondrial Dysfunction

“…A pyruvate tolerance test suggests the null animals had compromised hepatic gluconeogenesis. There was also a modest increase in hepatic CoA without a change in acetyl-CoA (Denis et al, 2019). Interestingly, this study did not identify major metabolic changes that were reported for the mNat1 null mice.…”

“…NAT1 and NAT2 both affect mitochondrial fuel usage and mitochondrial respiration, although the generality of these observations across different cells and tissues is currently not known (Chennamsetty et al, 2016;Denis et al, 2019;Wang et al, 2019). The paucity in work on co-expression of NAT1 and NAT2 emphasises the need to better understand how these proteins are regulated, whether their expressions are coordinated, and whether they show any functional redundancy.…”