Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Dec 18;12(12):3870.
doi: 10.3390/nu12123870.

Ketogenic Diet: Impact on Cellular Lipids in Hippocampal Murine Neurons

Partha Dabke  1 , Graham Brogden  2 , Hassan Y Naim  2 , Anibh M Das  1
Affiliations

Ketogenic Diet: Impact on Cellular Lipids in Hippocampal Murine Neurons

Partha Dabke et al. Nutrients. .

Abstract

Background: The mechanism of action of the ketogenic diet (KD), an effective treatment for pharmacotherapy refractory epilepsy, is not fully elucidated. The present study examined the effects of two metabolites accumulating under KD-beta-hydroxybutyrate (ßHB) and decanoic acid (C10) in hippocampal murine (HT22) neurons.

Methods: A mouse HT22 hippocampal neuronal cell line was used in the present study. Cellular lipids were analyzed in cell cultures incubated with high (standard) versus low glucose supplemented with ßHB or C10. Cellular cholesterol was analyzed using HPLC, while phospholipids and sphingomyelin (SM) were analyzed using HPTLC.

Results: HT22 cells showed higher cholesterol, but lower SM levels in the low glucose group without supplements as compared to the high glucose groups. While cellular cholesterol was reduced in both ßHB- and C10-incubated cells, phospholipids were significantly higher in C10-incubated neurons. Ratios of individual phospholipids to cholesterol were significantly higher in ßHB- and C10-incubated neurons as compared to controls.

Conclusion: Changes in the ratios of individual phospholipids to cholesterol in HT22 neurons suggest a possible alteration in the composition of the plasma membrane and organelle membranes, which may provide insight into the working mechanism of KD metabolites ßHB and C10.

Keywords: cholesterol; decanoic acid; hydroxybutyrate; ketogenic diet; neurons; phospholipids.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cellular cholesterol (µg/million cells) (A) and phospholipid (ng/million cells) quantities (B) in HT22 neurons. * p < 0.05 (n = 3–6); data are expressed as mean + SD. CL—cardiolipin; PC—phosphatidylcholine; PE—phosphatidylethanolamine; PS—phosphatidylserine; SM—sphingomyelin.
Figure 2
Figure 2
Cellular lipid quantities in HT22 neurons (control and ßHB-treated). Graph (A) represents cholesterol quantity (in µg per one million cells) measured using HPLC; graph (B) represents cellular phospholipid quantities (in ng per one million cells), measured using HPTLC; graph (C) represents the ratios of individual phospholipids to cholesterol in the control and beta-hydroxybutyrate-treated groups. Data are presented as mean + SD (n = 4–6); ** p < 0.01, *** p < 0.001. Chol—cholesterol; CL—cardiolipin; PC—phosphatidylcholine; PE—phosphatidylethanolamine; PL—phospholipid; PS—phosphatidylserine; SM—sphingomyelin.
Figure 3
Figure 3
Cellular lipid quantities in HT22 neurons (control and C10 treated). Graph (A) presents cholesterol quantity (in µg per one million cells) measured using HPLC; graph (B) presents cellular phospholipid quantities (in ng per one million cells), measured using HPTLC; graph (C) presents ratios of individual phospholipids to cholesterol in the control and beta-hydroxybutyrate-treated groups. Data are presented as mean + SD (n = 4–6); * p < 0.05, ** p < 0.01, *** p < 0.001. Chol—cholesterol; CL—cardiolipin; PC—phosphatidylcholine; PE—phosphatidylethanolamine; PL—phospholipid; PS—phosphatidylserine; SM—sphingomyelin.
Figure 4
Figure 4
ßHB—Beta-hydroxybutyrate; C10—Decanoic acid; Cho—Cholesterol; CL—Cardiolipin; CS—Citrate Synthase; IMM—Inner mitochondrial membrane; MRC—Mitochondrial Respiratory Chain (I—V are the individual complexes of the MRC); OMM—Outer mitochondrial membrane; PC—Phosphatidylcholine; PE—Phosphatidylethanolamine; PS—Phosphatidylserine; SIRT1—Sirtuin 1; SIRT3—Sirtuin 3; SM—Sphingomyelin. All red arrows depict the effects of ßHB, and all blue arrows depict the effects of C10. Thin arrows show already published data (adapted from [39]). Solid thick arrows show the effects of ßHB and C10 on absolute quantities of the depicted cellular lipids. Dotted thick arrows represent the effects of ßHB and C10 on ratios of the individual phospholipids (and sphingomyelin) to cellular cholesterol. Figure created with BioRender.com.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hamilton J.A., Hillard C.J., Spector A.A., Watkins P.A. Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins: Application to Neurological Disorders. J. Mol. Neurosci. 2007;33:2–11. doi: 10.1007/s12031-007-0060-1. - DOI - PubMed
    1. Tracey T.J., Steyn F.J., Wolvetang E.J., Ngo S.T. Neuronal Lipid Metabolism: Multiple Pathways Driving Functional Outcomes in Health and Disease. Front. Mol. Neurosci. 2018;11:10. doi: 10.3389/fnmol.2018.00010. - DOI - PMC - PubMed
    1. van Meer G., Voelker D.R., Feigenson G.W. Membrane lipids: Where they are and how they behave. Nat. Rev. Mol. Cell Biol. 2008;9:112–124. doi: 10.1038/nrm2330. - DOI - PMC - PubMed
    1. Blusztajn J.K., Liscovitch M., Mauron C., Richardson U.I., Wurtman R.J. Phosphatidylcholine as a precursor of choline for acetylcholine synthesis. J. Neural Transm. Suppl. 1987;24:247–259. - PubMed
    1. Fadeel B., Xue D. The ins and outs of phospholipid asymmetry in the plasma membrane: Roles in health and disease. Crit. Rev. Biochem. Mol. Biol. 2009;44:264–277. doi: 10.1080/10409230903193307. - DOI - PMC - PubMed

MeSH terms