ArticleThe Journal of biological chemistry2025
Anaplerosis by medium-chain fatty acids through complex interplay with glucose and glutamine metabolism.
Article in The Journal of biological chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Multi-omics analysis reveals the mechanism of enhanced GABA production in Lactiplantibacillus plantarum JY7 under acoustic and thermal coupling.Ultrasonics sonochemistry · 2026Article
- Strategic Targeting of Mitochondria: Bridging Biology and Therapy for Health Benefits.Cell biochemistry and biophysics · 2026Review
- Immunometabolic reprogramming in rheumatoid arthritis: the epitranscriptomic role of N6-methyladenosine in innate and adaptive immunity.Frontiers in immunology · 2026Review
- Molecular and cellular mechanisms of pentadecanoic acid.World journal of biological chemistry · 2025Review
- How Genes Meet Diet in LCHAD Deficiency: Nutrigenomics of Fatty Acid Oxidation Disorder.International journal of molecular sciences · 2025Review
- The Importance of Mitochondrial Processes in the Maturation and Acquisition of Competences of Oocytes and Embryo Culture.International journal of molecular sciences · 2025Review
- Matrix stiffness influences drug resistance to gemcitabine analog and AZD 1775 combination in PDAC organoids.PloS one · 2025Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The constant replenishment of tricarboxylic acid (TCA) cycle intermediates, or anaplerosis, is crucial to ensure optimal TCA cycle activity in times of high biosynthetic demand. In inborn metabolic diseases, anaplerosis is often affected, leading to impaired TCA cycle flux and ATP production. In these cases, anaplerotic compounds can be a therapy option. Triheptanoin, a triglyceride containing three heptanoate chains, is thought to be anaplerotic through production of propionyl- and acetyl-CoA. However, the precise mechanism underlying its anaplerotic action remains poorly understood. In this study, we performed a comprehensive in vitro analysis of heptanoate metabolism and compared it to that of octanoate, an even-chain fatty acid which only provides acetyl-CoA. Using stable isotope tracing, we demonstrate that both heptanoate and octanoate contribute carbon to the TCA cycle in HEK293 T cells, confirming direct anaplerosis. Furthermore, by using labeled glucose and glutamine, we show that heptanoate and octanoate decrease the contribution of glucose-derived carbon and increase the influx of glutamine-derived carbon into the TCA cycle. Our findings also point towards a change in redox homeostasis, indicated by an increased NAD
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Registered trials
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