Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 298, Issue 12, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jbc.2022.102648
Keywords
-
Categories
Funding
- National Institutes of Health
- [R01DK120530]
- [R01DK116746]
Ask authors/readers for more resources
In this study, liver-specific Pcx knockout mice (PcxL-/-) were generated to investigate the role of Pcx in hepatic mitochondrial metabolism under different physiological states. The results showed that hepatic Pcx is important for maintaining long-term glycemia under carbohydrate-limited diets, and loss of Pcx is associated with changes in the abundance of acetylated proteins.
Pyruvate has two major fates upon entry into mitochondria, the oxidative decarboxylation to acetyl-CoA via the pyruvate decarboxylase complex or the biotin-dependent carboxylation to oxaloacetate via pyruvate carboxylase (Pcx). Here, we have generated mice with a liver-specific KO of pyruvate carboxylase (PcxL-/-) to understand the role of Pcx in hepatic mitochon-drial metabolism under disparate physiological states. PcxL-/- mice exhibited a deficit in hepatic gluconeogenesis and enhanced ketogenesis as expected but were able to maintain systemic euglycemia following a 24 h fast. Feeding a high-fat diet to PcxL-/- mice resulted in animals that were resistant to glucose intolerance without affecting body weight. However, we found that PcxL-/- mice fed a ketogenic diet for 1 week became severely hypoglycemic, demonstrating a requirement for hepatic Pcx for long-term glycemia under carbohydrate -limited diets. Additionally, we determined that loss of Pcx was associated with an induction in the abundance of lysine-acetylated proteins in PcxL-/- mice regardless of physiologic state. Furthermore, liver acetyl-proteomics revealed a biased induction in mitochondrial lysine-acetylated proteins. These data show that Pcx is important for maintaining the proper balance of pyruvate metabolism between oxidative and anaplerotic pathways.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available