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Effect of one month duration ketogenic and non-ketogenic high fat diets on mouse brain bioenergetic infrastructure

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Abstract

Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain’s aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated.

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Acknowledgments

This project was supported by the University of Kansas Alzheimer’s Disease Center (NIH P30 AG035982), the University of Kansas Physician Scientist Training Program, the Frank and Evangeline Thompson Alzheimer’s Treatment Program fund, the Hugh and Betty Libby Foundation, the Greater Kansas City Automobile Dealers Association, and the Gene and Marge Sweeney Chair.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    J. Eva Selfridge & Russell H. Swerdlow

  2. Department of Neurology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA

    Heather M. Wilkins, Steven M. Carl, Scott Koppel, Eric Funk, Jianghua Lu & Russell H. Swerdlow

  3. Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Lezi E, WenFang Wang & Hao Zhu

  4. Department of Pathology, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Timothy Fields

  5. Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Ee Phie Tang, Chad Slawson, Hao Zhu & Russell H. Swerdlow

  6. Department of Clinical Laboratory Sciences, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    WenFang Wang & Hao Zhu

  7. University of Kansas Alzheimer’s Disease Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Russell H. Swerdlow

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  1. J. Eva Selfridge
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  2. Heather M. Wilkins
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  3. Lezi E
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  4. Steven M. Carl
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  5. Scott Koppel
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  6. Eric Funk
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  8. Jianghua Lu
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  9. Ee Phie Tang
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  10. Chad Slawson
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  11. WenFang Wang
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  12. Hao Zhu
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  13. Russell H. Swerdlow
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Correspondence to Russell H. Swerdlow.

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Selfridge, J.E., Wilkins, H.M., E, L. et al. Effect of one month duration ketogenic and non-ketogenic high fat diets on mouse brain bioenergetic infrastructure. J Bioenerg Biomembr 47, 1–11 (2015). https://doi.org/10.1007/s10863-014-9570-z

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  • DOI: https://doi.org/10.1007/s10863-014-9570-z

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