Metabolism of fatty acids and ketone bodies for glioblastoma growth: Implications for Ketogenic Diet Therapy

2019 ◽  
Author(s):  
Pablo Ranea Robles
iScience ◽  
2020 ◽  
Vol 23 (9) ◽  
pp. 101453
Author(s):  
Jantzen Sperry ◽  
Michael C. Condro ◽  
Lea Guo ◽  
Daniel Braas ◽  
Nathan Vanderveer-Harris ◽  
...  

2020 ◽  
Vol 18 (6) ◽  
pp. 35-40
Author(s):  
E.A. Pyrieva ◽  
◽  
A.I. Safronova ◽  
M.A. Toboleva ◽  
K.V. Osipova ◽  
...  

The article presents current dietetic approaches to organisation of a ketogenic diet (KD) in children with pharmacoresistant epilepsy. The indications, contraindications, side effects of KD are considered as well as methods of control over patients who receive ketogenic diet therapy, information recourses for it’s application are provided. Characteristics of KDs used in epilepsy are given – the classical, MCT, the Atkins modified diet, and a low-glycemic diet. The role of specialised food products designed for patients who need a ketogenic diet is outlined. The results of studying the actual nutrition of children with pharmacoresistant epilepsy who receive KD are indicative of a considerable decrease, as compared with the recommended allowances, of the levels of vitamins (С, В1, В2, folates, D3) and mineral substances (calcium, phosphorus, magnesium, iron, selenium). The results demonstrate good prospects for a broader application of KD in clinical practice with collaboration of neurologists and dietitians. Key words: children, ketogenic diet, ketone bodies, medium-chain triglycerides, epilepsy


Author(s):  
Carmen Murano ◽  
Anna Binda ◽  
Paola Palestini ◽  
Mirko Baruscotti ◽  
Jacopo C DiFrancesco ◽  
...  

In the last decade Ketogenic Diet (KD) came to light as a potential treatment for a wide range of diseases, from neurological to metabolic disorders, thanks to a beneficial role mainly related to its anti-inflammatory properties. The high-fat, carbohydrate-restricted regimen causes changes in the metabolism leading, through the β-oxidation of fatty acids, to the hepatic production of ketone bodies (KBs), used by many extrahepatic tissues as energy fuels. Once synthetized, KBs move through the systemic circulation and reach all the tissues of the organism, affecting their functions and playing pleiotropic roles acting directly and indirectly on various targets as ion channels and neurotransmitters. Moreover, they can operate as signalling metabolites and epigenetic modulators. Therefore, it is limiting to consider that the clinical condition of each single patient could improve after a KD regimen based on its localized effects; rather it is more complete to think about how KBs might affect the organism as a whole. In this minireview, we tried to summarize the recent knowledge of the effects of KBs on various tissues, with a particular attention to the excitable ones, namely the nervous system, heart and muscles.


Author(s):  
В.К. Поздеев

Кетогенная диета (КД) - это низкоуглеводная диета с высоким содержанием жиров и умеренным содержанием белков с включением витаминных комплексов, микро-, макроэлементов, особенно, кальция в сочетании с витамином D. У здорового человека при традиционном взвешенном питании углеводы, поступающие с пищей, перерабатываются в глюкозу, которая обеспечивает энергетическое питание и функционирование ЦНС. Посредством КД в рационе присутствует малое количество углеводов, поэтому печень компенсаторно, стремясь обеспечить организм энергетическим питанием, начинает интенсивно преобразовывать жир в жирные кислоты, затем в кетоновые тела - ацетоацетат, b-оксибутират, ацетон (кетогенез) в качестве альтернативы глюкозе. В результате, формируется состояние кетоза - повышенного уровня кетоновых тел в крови - и затем их утилизация в митохондриях периферических тканей и ЦНС (кетолизис). Одновременно происходит глубокое перепрограммирование метаболических процессов с терапевтическими (при эпилепсии и многих нейродегенеративных заболеваниях), или негативными последствиями при дефектах метаболизма жиров, функции печени и почек. КД изначально применялась (часто, с высоким терапевтическим эффектом) для лечения эпилептиформных состояний, вызванных дефектами энергетического метаболизма, у детей; затем у взрослых - ее облегченные модификации посредством умеренного повышения в рационе углеводов, белков, среднецепочечных жирных кислот. КД предусматривает (в соответствии с ростом и возрастом) достаточное количество калорий для поддержания нормальной массы тела, необходимое количество белков и минимальное количество углеводов для роста, регенерации организма. КД-терапия успешно используется при дефекте транспорта глюкозы (транспортера GLUT-1) в ЦНС, дефиците пируватдегидрогеназы; оказывает положительное действие при ожирении, диабете 2-го типа, болезнях Паркинсона и Альцгеймера, боковом амиотрофическом склерозе, рассеянном склерозе, инсультах, травмах и злокачествеенных опухолях головного мозга. Классическая КД противопоказана при нарушениях кетогенеза и кетолизиса, нарушениях функции печени и почек, недостаточности карнитин-пальмитоилтрансферазы I (транспортера жирных кислот в митохондрии), но ее модификации эффективны при некоторых дефектах обмена жиров. Ketogenic diet (KD) is a low carbohydrate diet that contains high amounts of fats and moderate amounts of proteins and includes vitamins, micro- and macroelements (particularly, calcium in combination with vitamin D). In a healthy human on traditional balanced diet, carbohydrates from food are being converted to glucose that provides energy for the central nervous system (CNS). KD contains little carbohydrates, therefore liver, to provide organism with energy, compensatory converts fat into fatty acids and then into ketone bodies acetoacetate, b-hydroxybutyrate, acetone as an alternative to glucose (ketogenesis). This results in ketosis - increased levels of ketone bodies in blood followed by their utilization in mitochondria of peripheral tissues and CNS (ketolysis). Simultaneously, a deep reprogramming of metabolic processes occurs resulting in therapeutic (in epilepsy and many neurodegenerative diseases) or negative (when fat metabolism defects or liver and kidney insufficiency are present) consequences. KD was initially used (frequently with therapeutic benefit) for the treatment of epileptiform conditions caused by defects in energy metabolism in children and later in adults (using lightened modifications with modestly increased levels of carbohydrates, proteins and medium-chain fatty acids). KD provides sufficient number of calories (matching patient’s height and age) to maintain normal body weight, necessary amount of protein and minimal amount of carbohydrates for organism growth and regeneration. KD is used successfully in patients with CNS glucose transport defects (GLUT-1), pyruvate dehydrogenase deficit, it provides benefits in obesity, type 2 diabetes, Parkinson’s and Alzheimer’s disease, lateral amyotrophic sclerosis, multiple sclerosis, stroke, traumas and brain malignancies, Classic KD is contraindicated in ketogenesis and ketolysis defects, liver insufficiency, kidney insufficiency, carnitine palmitoyltransferase I (mitochondrial fatty acid transporter) deficiency but its modifications are effective in some fat metabolism defects.


2019 ◽  
Author(s):  
Jantzen Sperry ◽  
Michael C. Condro ◽  
Lea Guo ◽  
Daniel Braas ◽  
Nathan Vanderveer-Harris ◽  
...  

SummaryGlioblastoma (GBM) metabolism has traditionally been characterized by a primary dependence on aerobic glycolysis, prompting the use of the ketogenic diet (KD) as a potential therapy. In this study we evaluated the effectiveness of the KD in GBM and assessed the role of fatty acid oxidation (FAO) in promoting GBM propagation. In vitro assays revealed FA utilization throughout the GBM metabolome, and growth inhibition in nearly every cell line in a broad spectrum of patient-derived glioma cells treated with FAO inhibitors. In vivo assessments revealed that knockdown of carnitine palmitoyltransferase 1A (CPT1A), the rate limiting enzyme for FAO, reduced the rate of tumor growth and increased survival. However, the unrestricted ketogenic diet did not reduce tumor growth, and for some models significantly reduced survival. Altogether, these data highlight important roles for FA and ketone body metabolism that could serve to improve targeted therapies in GBM.


Author(s):  
Huan Liu ◽  
Jingwei Huang ◽  
Hui Liu ◽  
Feng Li ◽  
Quansheng Peng ◽  
...  

Abstract Background The ketogenic diet (KD) can promote the anti-inflammatory metabolic state and increase ketone body level in rats. This study was to explore the effects and differences of KD with or without medium-chain fatty acids (MCFAs) on serum inflammatory factors and mTOR pathway in Sprague–Dawley (SD) rats. Results Male SD rats were assigned to five groups: control diet (C), 20% caloric restriction diet (LC), 20% caloric restriction ketogenic diet (containing MCFAs) (LCKD1), 20% caloric restriction ketogenic diet (LCKD2) and 20% caloric restriction foreign ketogenic diet (LCKD3), and fed for 30 d. LC and KD could significantly reduce the body weight of rats; LC and KD containing MCFAs showed anti-inflammatory effects; KD without MCFAs decreased the concentration of mTOR1, while KD containing MCFAs decreased the expression of AMPK, mtor1 and P70sk. Conclusions KD containing MCFAs showed better effects on the mTOR pathway and anti-inflammation than that without MCFAs.


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