Genetic ablation of aldehyde reductase (Akr1a) augments exercise endurance in mice via activation of the PGC-1α-involved pathway

Miku Takahashi, Takujiro Homma, Ken ichi Yamada, Satoshi Miyata, Osamu Nakajima, Junichi Fujii

Research output: Contribution to journalArticle

Abstract

Aims: Aldehyde reductase (AKR1A) is involved in the synthesis of ascorbic acid (AsA) as well as the detoxification of aldehydes. AKR1A−/− (KO) mice produce about 10% of the normal amounts of AsA compared to AKR1A+/+ (WT) mice. We investigated physiologic roles of AKR1A in running using the KO mice. Main methods: The KO mice were subjected to a treadmill test under either restricted AsA production or a sufficiency by supplementation and compared the results with those of WT mice. Contents of glucose, aspartate aminotransferase, AsA and free fatty acids in blood were measured. Glycogen contents were measured in the liver and skeletal muscle, and hepatic proteins were examined by immunoblot analyses. Key findings: Running performance was higher in the KO mice than the WT mice irrespective of the AsA status. After the exercise period, blood glucose levels were decreased in the WT mice but were preserved in the KO mice. Liver glycogen levels were also consistently preserved in the KO mice after exercise. Free fatty acid levels tended to be originally high in blood plasma compared to those of the WT mice and were increased to similar extent in them. A key regulator of energy metabolism, PGC-1α, and the products of downstream target genes that encode for glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphatase, were constitutively at high levels in the KO mice. Significance: The genetic ablation of AKR1A activates the PGC-1α pathway and spare glucose, which would consequently confer exercise endurance.

Original languageEnglish
Article number117501
JournalLife Sciences
Volume249
DOIs
Publication statusPublished - May 15 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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