Sleep profile during fasting in PPAR-alpha knockout mice

Kondo, Yoshitsugu; Chikahisa, Sachiko; Shiuchi, Tetsuya; Shimizu, Noriyuki; Tanioka, Daisuke; Uguisu, Haruo; Séi, Hiroyoshi

doi:10.1016/j.physbeh.2019.112760

Cited by 7 publications

(7 citation statements)

References 33 publications

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“…While some authors showed a lack of expression of HMGCS2 in astrocytes and neurons ( Thevenet et al, 2016 ), the latest studies confirm the astrocytic expression of HMGCS mRNA ( Song et al, 2021 ). HMGCS has been found to be abundantly expressed in the astrocytes of the optic nerve ( Metwally et al, 2019 ) and other glial cells ( Wang et al, 2016 ) and various brain areas ( Shao et al, 2019 ; Kondo et al, 2020 ), including the hippocampus ( Wang et al, 2020 ). Moreover, HMGCS2 has been defined as an autophagy regulator ( Hu et al, 2017 ), which raises the role of ketone metabolism as an autophagy enhancer.…”

Section: Discussionmentioning

confidence: 99%

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet

Liśkiewicz

Nowacka-Chmielewska

et al. 2021

Front. Cell. Neurosci.

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Experimental and clinical data support the neuroprotective properties of the ketogenic diet and ketone bodies, but there is still a lot to discover to comprehensively understand the underlying mechanisms. Autophagy is a key mechanism for maintaining cell homeostasis, and therefore its proper function is necessary for preventing accelerated brain aging and neurodegeneration. Due to many potential interconnections, it is possible that the stimulation of autophagy may be one of the mediators of the neuroprotection afforded by the ketogenic diet. Recent studies point to possible interconnections between ketone body metabolism and autophagy. It has been shown that autophagy is essential for hepatic and renal ketogenesis in starvation. On the other hand, exogenous ketone bodies modulate autophagy both in vitro and in vivo. Many regional differences occur between brain structures which concern i.e., metabolic responses and autophagy dynamics. The aim of the present study was to evaluate the influence of the ketogenic diet on autophagic markers and the ketone body utilizing and transporting proteins in the hippocampus and frontal cortex. C57BL/6N male mice were fed with two ketogenic chows composed of fat of either animal or plant origins for 4 weeks. Markers of autophagosome formation as well as proteins associated with ketolysis (BDH1—3-hydroxybutyrate dehydrogenase 1, SCOT/OXCT1—succinyl CoA:3-oxoacid CoA transferase), ketone transport (MCT1—monocarboxylate transporter 1) and ketogenesis (HMGCL, HMGCS2) were measured. The hippocampus showed a robust response to nutritional ketosis in both changes in the markers of autophagy as well as the levels of ketone body utilizing and transporting proteins, which was also accompanied by increased concentrations of ketone bodies in this brain structure, while subtle changes were observed in the frontal cortex. The magnitude of the effects was dependent on the type of ketogenic diet used, suggesting that plant fats may exert a more profound effect on the orchestrated upregulation of autophagy and ketone body metabolism markers. The study provides a foundation for a deeper understanding of the possible interconnections between autophagy and the neuroprotective efficacy of nutritional ketosis.

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Section: Discussionmentioning

confidence: 99%

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet

Liśkiewicz

Nowacka-Chmielewska

et al. 2021

Front. Cell. Neurosci.

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“…The results suggest that PPARα and KBs may play important roles in the maintenance of wakefulness under conditions of lack of energy supply. Mice with PPARα deficiency that underwent food deprivation showed increased sleepiness and amount of NREM sleep [ 68 ]. In a previous study, mice treated with bezafibrate, a pan PPAR agonist, had increased slow wave activity in NREM sleep and a higher KBs ratio (AcAc/BHB) [ 69 ].…”

Section: Resultsmentioning

confidence: 99%

The Influence of Ketone Bodies on Circadian Processes Regarding Appetite, Sleep and Hormone Release: A Systematic Review of the Literature

et al. 2022

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Chrononutrition is an emerging branch of chronobiology focusing on the profound interactions between biological rhythms and metabolism. This framework suggests that, just like all biological processes, even nutrition follows a circadian pattern. Recent findings elucidated the metabolic roles of circadian clocks in the regulation of both hormone release and the daily feeding–fasting cycle. Apart from serving as energy fuel, ketone bodies play pivotal roles as signaling mediators and drivers of gene transcription, promoting food anticipation and loss of appetite. Herein we provide a comprehensive review of the literature on the effects of the ketogenic diets on biological processes that follow circadian rhythms, among them appetite, sleep, and endocrine function.

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“…In the present study, the Ppara KO mice showed a significantly lowered PPI in the PPI test (at the prepulse levels of 70, 78 and 82) and excessive buried marbles in the marble-burying test. Furthermore, previous studies showed that the Ppara KO mice exhibited repetitive behavior and cognitive inflexibility [31] and altered sleep behavior during fasting [32] . These results indicate that PPARA deficiency may lead to vulnerability to schizophrenia and other mental conditions such as autism.…”

Section: Discussionmentioning

confidence: 97%

“…These prodromal phenotypes of schizophrenia resulting from the dysregulated transcription of neurodevelopment-related genes are accompanied by reduced expression of Ppara (encoding the PPARα subtype) and Rxra (encoding the RXRα subtype) genes in the mouse cortex [24] . Moreover, Ppara -deficient mice have shown repetitive behavior and cognitive inflexibility [31] , and altered sleep profiles when subjected to dietary restrictions [32] . Furthermore, the role of Ppara in hippocampal synaptogenesis also suggests its potential role in neuronal function [ 19 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor α as a novel therapeutic target for schizophrenia

et al. 2020

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Sleep profile during fasting in PPAR-alpha knockout mice

Cited by 7 publications

References 33 publications

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet

The Influence of Ketone Bodies on Circadian Processes Regarding Appetite, Sleep and Hormone Release: A Systematic Review of the Literature

Peroxisome proliferator-activated receptor α as a novel therapeutic target for schizophrenia

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