title: Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis.
abstract: Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.
authors.affiliation: Medical University of Silesia, School of Medicine in Katowice, Department of Physiology, Katowice, Poland.|Affective Cognitive Neuroscience Lab, Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology Polish Academy of Sciences Krakow, Poland.
authors.forename: Arkadiusz D
authors.initials: AD
authors.lastname: Liśkiewicz
authors.affiliation: Medical University of Silesia, School of Medicine in Katowice, Department of Pharmacology, Katowice, Poland.|Laboratory of Molecular Biology, Faculty of Physiotherapy, The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kasprowska
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wojakowska
authors.affiliation: Warwick Systems Biology Centre, University of Warwick, CV4 7AL, UK.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Polański
authors.affiliation: Medical University of Silesia, School of Medicine in Katowice, Department of Physiology, Katowice, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Lewin-Kowalik
authors.affiliation: Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kotulska
authors.affiliation: Medical University of Silesia, School of Medicine in Katowice, Department of Physiology, Katowice, Poland.
authors.forename: Halina
authors.initials: H
authors.lastname: Jędrzejowska-Szypułka
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000209:etiology / Q000473:pathology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D055423:Diet, Ketogenic / Q000009:adverse effects*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D007680:Kidney Neoplasms / Q000097:blood / Q000209:etiology / Q000473:pathology*; D008297:Male; D019301:Oleic Acid / Q000378:metabolism; D020318:Rats, Long-Evans; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000097:blood / Q000178:diet therapy*; D047368:Tumor Burden
chemical_list: D007328:Insulin; C548904:insulin-like growth factor-1, rat; D019301:Oleic Acid; D007334:Insulin-Like Growth Factor I; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases