Differential Metabolism of Medium-Chain Fatty Acids in Differentiated Human-Induced Pluripotent Stem Cell-Derived Astrocytes.

Sonnay, Sarah; Chakrabarti, Anirikh; Thevenet, Jonathan; Wiederkehr, Andreas; Christinat, Nicolas; Masoodi, Mojgan (2019). Differential Metabolism of Medium-Chain Fatty Acids in Differentiated Human-Induced Pluripotent Stem Cell-Derived Astrocytes. Frontiers in physiology, 10(657), p. 657. Frontiers Research Foundation 10.3389/fphys.2019.00657

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Medium-chain triglyceride (MCT) ketogenic diets increase ketone bodies, which are believed to act as alternative energy substrates in the injured brain. Octanoic (C8:0) and decanoic (C10:0) acids, which produce ketone bodies through β-oxidation, are used as part of MCT ketogenic diets. Although the ketogenic role of MCT is well-established, it remains unclear how the network metabolism underlying β-oxidation of these medium-chain fatty acids (MCFA) differ. We aim to elucidate basal β-oxidation of these commonly used MCFA at the cellular level. Human-induced pluripotent stem cell-derived (iPSC) astrocytes were incubated with [U-13C]-C8:0 or [U-13C]-C10:0, and the fractional enrichments (FE) of the derivatives were used for metabolic flux analysis. Data indicate higher extracellular concentrations and faster secretion rates of β-hydroxybutyrate (βHB) and acetoacetate (AcAc) with C8:0 than C10:0, and an important contribution from unlabeled substrates. Flux analysis indicates opposite direction of metabolic flux between the MCFA intermediates C6:0 and C8:0, with an important contribution of unlabeled sources to the elongation in the C10:0 condition, suggesting different β-oxidation pathways. Finally, larger intracellular glutathione concentrations and secretions of 3-OH-C10:0 and C6:0 were measured in C10:0-treated astrocytes. These findings reveal MCFA-specific ketogenic properties. Our results provide insights into designing different MCT-based ketogenic diets to target specific health benefits.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Masoodi, Mojgan

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-042X

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Mojgan Masoodi

Date Deposited:

14 Nov 2019 08:00

Last Modified:

13 Mar 2021 14:07

Publisher DOI:

10.3389/fphys.2019.00657

PubMed ID:

31214043

Uncontrolled Keywords:

13C-metabolic flux analysis decanoic acid induced pluripotent stem cell-derived astrocytes octanoic acid β-oxidation

BORIS DOI:

10.7892/boris.134955

URI:

https://boris.unibe.ch/id/eprint/134955

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