Hepatic NADH reductive stress underlies common variation in metabolic traits.

ABSTRACT: The cellular NADH/NAD⁺ ratio is fundamental to biochemistry, but the extent to which it reflects versus drives metabolic physiology in vivo is poorly understood. Here we report the in vivo application of Lactobacillus brevis (Lb)NOX¹, a bacterial water-forming NADH oxidase, to assess the metabolic consequences of directly lowering the hepatic cytosolic NADH/NAD⁺ ratio in mice. By combining this genetic tool with metabolomics, we identify circulating α-hydroxybutyrate levels as a robust marker of an elevated hepatic cytosolic NADH/NAD⁺ ratio, also known as reductive stress. In humans, elevations in circulating α-hydroxybutyrate levels have previously been associated with impaired glucose tolerance², insulin resistance³ and mi

SUBMITTER: Goodman RP 

PROVIDER: S-EPMC7536642 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature