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1

Long term treatment of ketogenic diet increases kidney tumor growth by p53-dependent manner

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Liskiewicz A., Kasprowska-Liskiewicz D., Lewin-Kowalik J., Jedrzejowska-Szypulska H.
Acta Neurobiologiae Experimentalis
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2014
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tom 74
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nr 3
The Eker rat is a useful model of tuberous sclerosis, genetic disease with leads to tumor growth in many tissues. Ketogenic diet (KD) is already used in treatment of epilepsy in tuberous sclerosis patients, but its influence on tumor growth is still not clear. Here we reported how KD affects growth of kidney tumors in Eker rats, subjected to the diet for 4, 6 and 8 months. Data were compared to animals fed with standard diet. Obtained results showed that long term treatment of ketogenic diet promotes tumor growth in kidneys. Additionally, biochemical analysis of renal tissue indicate a possible mechanism in growth promoting influence of KD by lowering p53 protein, guardian of the genome.
2

Solid pituitary adenoma in Eker rats subjected to ketogenic diet

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Liskiewicz A., Gendosz D., Jedrzejowska-Szypulka H., Lewin-Kowalik J.
Acta Neurobiologiae Experimentalis
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2013
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tom 73
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nr Suppl.1
Tuberous sclerosis (TS) is a genetic disease causing non-malignant tumors growth in the brain (e.g. pituitary adenoma) and in other organs. Ketogenic diet is already used in TS patients in treatment of epilepsy. However the mechanism of its influence on tumor growth is still not clear. The Eker rat is a useful model of TS: it has a spontaneous germ line mutation of the TSC2 gene what predisposed them to multiple tumors. In Eker rats, pituitary adenomas are common, occurring in 58% of adults (more than 18-months-old). Methods: Forty six 8-month-old Eker rats (males and females) were used. Twenty six (experimental group) have been maintained on high fat, low carbohydrate ketogenic diet for 6 months, while 20 (control group) received a standard rodent diet. At the age of 14 months rats were sacrificed. Anteroposterior, vertical, and transverse diameters of the found pituitary adenomas were measured. Size of tumors was calculated by using the formula for volume of the ellipsoid. Results: 8% animals from experimental group and 20% from control group have developed pituitary adenomas. Mean tumor volume in experimental group was 143 mm2 vs. 217 mm2 in control animals. Conclusion: Eker rats fed with ketogenic diet develops solid pituitary adenoma in 14 months of age. Incidence of these pituitary tumors in Eker rats fed with ketogenic diet (8%) was lower when compared with rats from control group (20%).
3

Anxiety-like behavior of laboratory animals on a ketogenic diet

64%
Przybyla M., Liskiewicz D., Nowacka-Chmielewska M., Liskiewicz A., Grajoszek A., Grabowski M., Jablonska K., Barski J. J.
Acta Neurobiologiae Experimentalis
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2019
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tom 79
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nr Suppl.1
INTRODUCTION: In the recent years, more attention is attributed to the impact of diet on central nervous system function. An increasing number of diseases, including neurological disorders, results from inadequate dietary habits. Diet, however, can affect the function of brain and mental processes in a negative as well as a beneficial way. The diet with well‑documented neuroprotective effects is a high-fat and low-carbohydrate ketogenic diet (KD). METHOD(S): We investigated two type of KD, one of them based on animal (KDA), while the other on vegetable fats (KDB). Both diets were applied to two groups of laboratory animals: mice (129S2/SvPasCrl) and rats (Long‑Evans Rat, Crl: LE) for 6 weeks. CONCLUSIONS: Interestingly, preliminary data indicate a unique anxiogenic action of the KD but only in mice.
4

Ketogenic diets based on fat of either animal or plant origin have different effects on the abundance of autophagic vesicles in mouse brain

64%
Liskiewicz D., Liskiewicz A., Nowacka-Chmielewska M., Jablonska K., Grabowski M., Student S., Slugocka A., Przybyla M., Barski J. J., Malecki A.
Acta Neurobiologiae Experimentalis
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2019
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tom 79
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nr Suppl.1
INTRODUCTION: Autophagy is a cellular recycling mechanism essential for maintenance of cell homeostasis and viability, especially during stress conditions; hence, autophagy is involved in a number of physiological and pathological processes. Autophagy is thought to be involved in anti‑aging and neuroprotective effects of caloric restriction, Sirtuin 1 activation, inhibition of insulin/ insulin-like growth factor signaling, and administration of rapamycin, resveratrol, and metformin. The ketogenic diet mimics the biochemical actions of fasting and exerts many physiological and cellular responses similar to those evoked by intermittent energy restriction. Despite this, the relationship between nutritional ketosis and autophagy has been a largely unexplored field. AIM(S): The aim of this study was to verify the hypothesis that ketogenic diets affect the process of autophagosome formation in the hippocampus and/or cerebral cortex. METHOD(S): 9-week-old male mice were fed with one of two differently composed ketogenic chows – based on the fat of either animal or plant origin (KA, KP respectively) or with standard rodent chow (SD) – for 6 subsequent weeks. Western blotting, (LC3, p62), QRT‑PCR (LC3A, LC3B, p62), and confocal microscopy (LC3 puncta) were employed to monitor autophagy in hippocampal and cerebrocortical samples. RESULTS: Western blot results revealed increased levels of LC3 II protein – a marker of autophagosomes – in the hippocampus and frontal cortex of mice treated with the ketogenic diet. This observation was confirmed by the evaluation of a number of LC3 puncta with immunofluorescence microscopy. The size of this effect was dependent on the composition of the diet. CONCLUSIONS: This study reports, for the first time, an upregulation of autophagosome synthesis in the brain of animals fed with the ketogenic diet. Our results make a significant contribution to the understanding of the mechanisms of ketogenic diet action. FINANCIAL SUPPORT: This research is supported by the National Science Center grant no. 2017/01/X/ NZ3/00984.
5

Global proteomic analysis of brain changes induced by 'lifestyle' modifications

64%
Nowacka-Chmielewska M., Liskiewicz D., Liskiewicz A., Marczak L., Wojakowska A., Przybyla M., Grabowski M., Jablonska K., Barski J. J., Malecki A.
Acta Neurobiologiae Experimentalis
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2019
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tom 79
|
nr Suppl.1
In the pathogenesis of central nervous system (CNS) disorders, an increasingly important role is attributed recently to unhealthy lifestyle, which consists primarily of a high caloric diet (i.e., western), chronic exposure to stress, and lack of physical activity. However, the mechanisms responsible for energy metabolism impairment induced by unhealthy lifestyles compromising CNS functions are poorly understood. Research on the effects of physical activity on the CNS is especially important, because it may result in the development of new methods of therapy inspired by natural protective mechanisms. In our study we employed a new and rarely used approach – a forced running wheel. The lack of electrical stimulus in the aforementioned system successfully makes a breakthrough in the study of animal physical activity. Physiological and behavioral responses of the organism to stress are closely related to sex. Epidemiological studies indicate that women are more vulnerable to the adverse effects of stress and despite that, most of the experimental studies are conveyed on male animals. The investigations were carried on female rats. The main goal of our study was to verify the hypothesis that regular exercise may reduce the disturbances induced by lifestyle modifications, like western diet and/or stress exposure. Adult female rats were fed with the prepared chow reproducing the human western diet and/or subjected to a stress induced by social instability. This stress protocol is characterized by a low degree of invasiveness. To evaluate if regular physical activity may reduce the adverse effects caused by diet and stress, female rats were additionally subjected to the procedure of forced physical activity. A proteomic analysis was conducted on samples obtained from the frontal cortex – a region that plays an important role in cognitive processes as well as is involved in the mechanisms engaged in the response to stress.
6

Anxiolytic effect of physical activity and cerebral accumulation of saturated fatty acids

52%
Liskiewicz A., Przybyla M., Wojakowska A., Marczak L., Bogus K., Nowacka-Chmielewska M., Liskiewicz D., Malecki A., Barski J. J., Lewin-Kowalik J., Toborek M.
Acta Neurobiologiae Experimentalis
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2019
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tom 79
|
nr Suppl.1
INTRODUCTION: The broad spectrum of the positive effects of physical activity on brain functioning is well acknowledged. Among others, it induces an improvement in mood, and a part of the rodent studies support this thesis by showing anxiolytic effects of exercise. However, the mechanism of this behavioral modification is not clear. Changes in brain metabolism may contribute to the generation of complex brain disorder phenotypes; thus, metabolomics have proven to be useful tools in studies on the central nervous system. AIM(S): The discrimination of anxiolytic level and metabolomics changes in the brain were evaluated in this study. METHOD(S): Voluntary running mice were subjected to a battery of behavioral tests (Open Field, Elevated Plus Maze, Dark/Light Box) commonly used to measure anxiety levels. Simultaneously, GC/MS analysis of hippocampal and cortical samples was performed for metabolome profiling of the running mice. RESULTS: The exercised animals showed anxiolytic behavior. Voluntary running caused an accumulation of saturated fatty acids, such as myrisitc, palmitic, heptadecanoic, and stearic acids, in the hippocampus and cortex of running mice. CONCLUSIONS: A striking observation in the present study is that a profile of saturated fatty acids that accumulates in the hippocampi and cortex of the running mice is consistent with the mixture of fatty acids that was identified as causing anxiolytic-like effects when administered to rodents.
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