Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis

Sci Rep. 2016 Feb 19;6:21807. doi: 10.1038/srep21807.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / etiology
  • Carcinoma, Renal Cell / pathology*
  • Diet, High-Fat / adverse effects*
  • Diet, Ketogenic / adverse effects*
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Insulin / blood
  • Insulin-Like Growth Factor I / metabolism
  • Kidney / enzymology
  • Kidney / pathology
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / etiology
  • Kidney Neoplasms / pathology*
  • Male
  • Oleic Acid / metabolism
  • Rats, Long-Evans
  • TOR Serine-Threonine Kinases / metabolism
  • Tuberous Sclerosis / blood
  • Tuberous Sclerosis / diet therapy*
  • Tumor Burden

Substances

  • Insulin
  • insulin-like growth factor-1, rat
  • Oleic Acid
  • Insulin-Like Growth Factor I
  • TOR Serine-Threonine Kinases
  • mTOR protein, rat
  • Extracellular Signal-Regulated MAP Kinases