title: Effect of one month duration ketogenic and non-ketogenic high fat diets on mouse brain bioenergetic infrastructure.
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.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
authors.forename: J Eva
authors.initials: JE
authors.lastname: Selfridge
authors.forename: Heather M
authors.initials: HM
authors.lastname: Wilkins
authors.forename: Lezi
authors.initials: L
authors.lastname: E
authors.forename: Steven M
authors.initials: SM
authors.lastname: Carl
authors.forename: Scott
authors.initials: S
authors.lastname: Koppel
authors.forename: Eric
authors.initials: E
authors.lastname: Funk
authors.forename: Timothy
authors.initials: T
authors.lastname: Fields
authors.forename: Jianghua
authors.initials: J
authors.lastname: Lu
authors.forename: Ee Phie
authors.initials: EP
authors.lastname: Tang
authors.forename: Chad
authors.initials: C
authors.lastname: Slawson
authors.forename: WenFang
authors.initials: W
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.forename: Russell H
authors.initials: RH
authors.lastname: Swerdlow
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000378:metabolism; D055423:Diet, Ketogenic / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects*; D004734:Energy Metabolism / Q000187:drug effects*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004272:DNA, Mitochondrial; D004041:Dietary Fats; D009419:Nerve Tissue Proteins
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