Ketone bodies have been regarded as an energy source that is mainly produced in the liver, and exported to extrahepatic tissues. However, ketone bodies have also been suggested to be used during the lipogenesis by the ketone body-utilizing enzyme, acetoacetyl-CoA synthetase (AACS). To elucidate the physiological role of AACS in the liver, we investigated the mechanism of transcription of the AACS gene and performed knockdown experiments. We showed that SREBP-2 regulates the expression of AACS and that knockdown of AACS in vivo, by the hydrodynamics method, resulted in the reduction of total blood cholesterol. These results suggest that ketone body metabolism via AACS activity plays an important role in cholesterol homeostasis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ymgme.2012.08.017 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An alternative route for β-hydroxybutyrate metabolism supports fatty acid synthesis in cancer cells.
bioRxiv
November 2024
Department of Metabolism and Nutritional Programming, Van Andel Institute, 333 Bostwick Ave. NE, Grand Rapids, MI 49503.
Cancer cells are exposed to diverse metabolites in the tumor microenvironment that are used to support the synthesis of nucleotides, amino acids, and lipids needed for rapid cell proliferation. Recent work has shown that ketone bodies such as β-hydroxybutyrate (β-OHB), which are elevated in circulation under fasting conditions or low glycemic diets, can serve as an alternative fuel that is metabolized in the mitochondria to provide acetyl-CoA for the tricarboxylic acid (TCA) cycle in some tumors. Here, we discover a non-canonical route for β-OHB metabolism, in which β-OHB can bypass the TCA cycle to generate cytosolic acetyl-CoA for fatty acid synthesis in cancer cells.
View Article and Find Full Text PDFIdentification of the Regulatory Elements and Protein Substrates of Lysine Acetoacetylation.
bioRxiv
October 2024
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, USA.
Short chain fatty acylations establish connections between cell metabolism and regulatory pathways. Lysine acetoacetylation (Kacac) was recently identified as a new histone mark. However, regulatory elements, substrate proteins, and epigenetic functions of Kacac remain unknown, hindering further in-depth understanding of acetoacetate modulated (patho)physiological processes.
View Article and Find Full Text PDFA hierarchical hepatic de novo lipogenesis substrate supply network utilizing pyruvate, acetate, and ketones.
Cell Metab
January 2025
Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Fraternal Order of Eagles Diabetes Research Center (FOEDRC), University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; FOEDRC Metabolomics Core Research Facility, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Pappajohn Biomedical Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA. Electronic address:
Hepatic de novo lipogenesis (DNL) is a fundamental physiologic process that is often pathogenically elevated in metabolic disease. Treatment is limited by incomplete understanding of the metabolic pathways supplying cytosolic acetyl-CoA, the obligate precursor to DNL, including their interactions and proportional contributions. Here, we combined extensive C tracing with liver-specific knockout of key mitochondrial and cytosolic proteins mediating cytosolic acetyl-CoA production.
View Article and Find Full Text PDFKetone body oxidation and susceptibility to ethyl acetoacetate in a novel hemolytic multidrug-resistant strain Leptospira interrogans KeTo originated from sewage water.
Sci Rep
October 2024
Division of Microbiology and Biotechnology, Yenepoya (Deemed to be University), Yenepoya Research Centre, University Road, Deralakatte, Mangalore, 575018, India.
Article Synopsis
- Terrestrial and aquatic environments contaminated with animal urine can spread Leptospira, which causes leptospirosis in both humans and animals, but the factors influencing its growth and virulence are not fully understood.
- A new strain of Leptospira interrogans, named KeTo, was isolated from sewage in India and can oxidize various organic acids, demonstrating susceptibility to ethyl acetoacetate that inhibits its growth and biofilm formation.
- Genetic analysis revealed that KeTo shares a high similarity to pathogenic strains and has specific genes for utilizing acetoacetate, indicating its metabolic capabilities and the need for further research on its growth inhibition.
A single Leishmania adenylate-forming enzyme of the ANL superfamily generates both acetyl- and acetoacetyl-CoA.
J Biol Chem
November 2024
Department of Pediatrics Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA; Microbiology/Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. Electronic address:
Article Synopsis
- Leishmania is a protozoan parasite that causes serious diseases such as cutaneous and visceral leishmaniasis, heavily impacting impoverished communities with limited medical resources.
- Current treatments are toxic and not very effective, prompting the need for research into the parasite's metabolism to find new drug targets.
- The study focused on the unique enzyme LiAcs1 from Leishmania infantum, which has both acetyl-CoA synthetase and acetoacetyl-CoA synthetase activities, revealing it as a promising target for developing selective inhibitors to disrupt the parasite's critical metabolic pathways.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!