Affichage des articles dont le libellé est régime kétogène. Afficher tous les articles
Affichage des articles dont le libellé est régime kétogène. Afficher tous les articles

22 mai 2017

Le régime cétogène conduit à une modification de O-GlcNAc dans le modèle de souris BTBRT + tf / j de l'autisme

Aperçu: G.M.
La protéine O-linked-β-N-acétyl glucosamine (O-GlcNAc) est une modification post-traductionnelle des résidus Ser / Thr qui intègre l'approvisionnement en énergie avec la demande. Le schéma anormal de l'O-GlcNAc est évident dans plusieurs états pathologiques neurologiques, y compris l'épilepsie, la maladie d'Alzheimer et le trouble du spectre de l'autisme (TSA). Une option de traitement potentielle pour ces troubles comprend le régime cétogène à haute teneur en matières grasses et à faible teneur en glucides (KD). L'objectif de cette étude était de déterminer si le KD induit des changements dans O-GlcNAc dans le modèle de souris BTBRT + tf / j (BTBR) du TSA.
Le KD a réduit l'O-GlcNAc global dans le foie de tous les animaux (p <0,05). Les réductions ont probablement été médiées par la diminution des taux de protéines de O-GlcNAc transferase (OGT) et par O-GlcNAcase (OGA) (p <0,05). En revanche, aucune différence dans l'O-GlcNAc globale n'a été observée dans le cerveau (p> 0,05), mais l'expression OGT et OGA (ARNm) était élevée chez les animaux C57 et BTBR (p <0,05). 
Le KD a des effets spécifiques sur les tissus sur O-GlcNAc. Bien que les niveaux d'O-GlcNAc jouent un rôle important dans le développement neurologique, les niveaux de cette modification dans le cerveau de souris juvénile étaient stables avec le KD malgré de grandes fluctuations de l'état énergétique. Cela suggère qu'il est peu probable que le KD exerce un avantage thérapeutique dans le modèle BTBR de TSA par les voies liées à O-GlcNAc. 

Biochim Biophys Acta. 2017 May 11. pii: S0925-4439(17)30150-3. doi: 10.1016/j.bbadis.2017.05.013.

Ketogenic diet leads to O-GlcNAc modification in the BTBRT+tf/j mouse model of autism

Author information

1
Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada; Department of Medical Science, University of Calgary Cumming School of Medicine, Calgary, AB, Canada. Electronic address: cnewell@ucalgary.ca.
2
Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.
3
Alberta Children's Hospital Research Institute, University of Calgary Cumming School of Medicine, Alberta Children's Hospital, AB, Canada.
4
Department of Medical Science, University of Calgary Cumming School of Medicine, Calgary, AB, Canada.
5
Alberta Children's Hospital Research Institute, University of Calgary Cumming School of Medicine, Alberta Children's Hospital, AB, Canada; Department of Medical Genetics and Pediatrics, University of Calgary Cumming School of Medicine, Alberta Children's Hospital, AB, Canada.
6
Alberta Children's Hospital Research Institute, University of Calgary Cumming School of Medicine, Alberta Children's Hospital, AB, Canada; Department of Paediatrics, University of Calgary Cumming School of Medicine, Alberta Children's Hospital, Calgary, AB, Canada; Department of Clinical Neurosciences, University of Calgary Cumming School of Medicine, Alberta Children's Hospital, Calgary, AB, Canada; Department of Physiology & Pharmacology, University of Calgary Cumming School of Medicine, Alberta Children's Hospital, Calgary, AB, Canada.
7
Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada; Department of Medical Science, University of Calgary Cumming School of Medicine, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, University of Calgary Cumming School of Medicine, Alberta Children's Hospital, AB, Canada.

Abstract

BACKGROUND:

Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model of ASD.

METHODS:

Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status.

RESULTS:

The KD reduced global O-GlcNAc in the livers of all animals (p<0.05). Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05).

CONCLUSIONS:

The KD has tissue specific impacts on O-GlcNAc. Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. This suggests that it is unlikely that the KD exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related pathways.

PMID: 28502704
DOI: 10.1016/j.bbadis.2017.05.013

01 avril 2017

Le régime kétogène et les troubles neurologiques de l'enfance autres que l'épilepsie: une vue d'ensemble

Aperçu: G.M.
Au cours des dernières années, le régime kétogène (KD) a été utilisé expérimentalement dans divers troubles neurologiques de l'enfance tels que les mitochondriopathies, l'hémiplégie alternée de l'enfance (AHC), les tumeurs cérébrales, la migraine et le trouble du spectre de l'autisme (TSA).
L'étude visait à analyser comment le KD peut cibler ces différentes conditions médicales, mettant en évidence les possibles mécanismes impliqués.
Le KD pourrait améliorer les compétences cognitives et sociales dans un sous-ensemble d'enfants avec un diagnostic de TSA

Expert Rev Neurother. 2017 May;17(5):461-473. doi: 10.1080/14737175.2017.1260004. Epub 2016 Nov 21.

Ketogenic diet and childhood neurological disorders other than epilepsy: an overview

Author information

1
a Department of Pediatrics , University of L'Aquila, San Salvatore Hospital , L'Aquila , Italy.
2
b Department of Child and Adolescent Neuropsychiatry , University of Salerno , Salerno , Italy.
3
c Department of Child Neuropsychiatry , University of Salerno , Salerno , Italy.

Abstract

INTRODUCTION:

In the last years, ketogenic diet (KD) has been experimentally utilized in various childhood neurologic disorders such as mitochondriopathies, alternating hemiplegia of childhood (AHC), brain tumors, migraine, and autism spectrum disorder (ASD). The aim of this review is to analyze how KD can target these different medical conditions, highlighting possible mechanisms involved. Areas covered: We have conducted an analysis on literature concerning KD use in mitochondriopathies, AHC, brain tumors, migraine, and ASD. Expert commentary: The role of KD in reducing seizure activity in some mitochondriopathies and its efficacy in pyruvate dehydrogenase deficiency is known. Recently, few cases suggest the potentiality of KD in decreasing paroxysmal activity in children affected by AHC. A few data support its potential use as co-adjuvant and alternative therapeutic option for brain cancer, while any beneficial effect of KD on migraine remains unclear. KD could improve cognitive and social skills in a subset of children with ASD.
PMID: 27841033
DOI: 10.1080/14737175.2017.1260004