Functional loss of ketogenesis in odontocete cetaceans.
Michael J WolfgangJoseph ChoiSusanna ScafidiPublished in: The Journal of experimental biology (2021)
Odontocete cetaceans exhibit genomic mutations in key ketogenesis genes. In order to validate an inferred lack of ketogenesis made by observations from genome sequencing, we biochemically analyzed tissues from several odontocete cetacean species and demonstrate that they indeed do not exhibit appreciable hepatic β-hydroxybutyrate (βHB) or its carnitine ester. Furthermore, liver tissue exhibited significantly lower long chain acylcarnitines and increased odd chain acylcarnitines indicative of a decreased reliance on hepatic long chain fatty acid oxidation in these carnivorous mammals. Finally, we performed single molecule, real-time next generation sequencing of liver and brain RNA of Tursiops truncatus and demonstrate that the succinyl-CoA transferase required for acetoacetate catabolism is expressed in the nervous system. These data show that odontocete cetaceans have lost the ability to perform ketogenesis and suggest a hepatocentric coenzyme A recycling function rather than a predominantly systemic-bioenergetic role for ketogenesis in other ketogenic competent mammals such as humans.
Keyphrases
- single molecule
- fatty acid
- copy number
- genome wide
- gene expression
- atomic force microscopy
- electronic health record
- big data
- machine learning
- single cell
- resting state
- deep learning
- blood brain barrier
- functional connectivity
- cell free
- genome wide identification
- white matter
- circulating tumor
- nucleic acid
- genetic diversity
- electron transfer