Progressive alterations in amino acid and lipid metabolism correlate with peripheral neuropathy in Polg^D257A mice.

ABSTRACT: Mitochondria are central to metabolic homeostasis, and progressive mitochondrial defects have diverse metabolic consequences that could drive distinct pathophysiological states. Here, we comprehensively characterized metabolic alterations in Polg^D257A mice. Plasma alanine increased markedly with time, with other organic acids accumulating to a lesser extent. These changes were reflective of increased Cori and Cahill cycling in Polg^D257A mice and subsequent hypoglycemia, which did not occur during normal mouse aging. Tracing with [¹⁵N]ammonium further supported this shift in amino acid metabolism with mild impairment of the urea cycle. We also measured alterations in the lipidome, observing a reduction in canonical lipids and accumulation of 1-

SUBMITTER: Lim EW 

PROVIDER: S-EPMC8519573 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature