Dieta cetogênica aumenta atividade do PPAR-alfa e promove efeito

anti-câncer

04/02/11

A dieta cetogênica com restrição de carboidratos aumenta a atividade do PPAR-alfa (peroxisome proliferator activated receptor alfa)que antagoniza o Akt e o c-Myc reduzindo assim o consumo celular de glicose e glutamina.A dieta cetogênica aumenta a razão NAD+/NADH que estimula a atividade da SIRT1 (sirtuin-protein deacetilase 1) e diminui a razãoATP/AMP que ativa a AMPK (AMP-dependent protein kinase) ambos os efeitos provocam o aumento da oxidação de ácidos graxos ea diminuição da síntese de proteínas,ácidos graxos e nucleotídeos com bloqueio da glicólise anaeróbia , via PGC-1alfa (PPAR gama1alfa). Este coopera com o PPAR-alfa nos seus efeitos anti-câncer da dieta cetogênica com restrição de carboidratos. Vários trabalhosna literatura já utilizaram este tipo de dieta no tratamento do câncer humano com resultados positivos. Jose de Felippe Junior

Peroxisome Proliferator Activated Receptor α Ligands As Anti-Cancer Drugs Targeting Mitochondrial Metabolism.Grabacka M, Pierzchalska M, Reiss K. Curr Pharm Biotechnol. 2010 Dec 6.Department of Food Biotechnology, Faculty of Food Technology, University of Agriculture, Krakow 30-149, ul. Balicka 122, Poland.maja.grabacka@ur.krakow.pl.AbstractTumor cells show metabolic features distinctive from normal tissues, with characteristic enhanced aerobic glycolysis, glutaminolysis andlipid synthesis. Peroxisome proliferator activated receptor α (PPAR α) is activated by nutrients (fatty acids and their derivatives) andinfluences these metabolic pathways acting antagonistically to oncogenic Akt and c-Myc activities. Therefore PPAR α can be regarded asa candidate target molecule in supplementary anti-cancer pharmacotherapy as well as dietary therapeutic approach. This idea is basedon hitting the cancer cell metabolic weak points through PPAR α mediated stimulation of mitochondrial fatty acid oxidation andketogenesis with simultaneous reduction of glucose and glutamine consumption. PPAR α activity is induced by fasting and its molecularconsequences overlap with the effects of calorie restriction and ketogenic diet (CRKD). CRKD induces increase of NAD(+)/NADH ratioand drop in ATP/AMP ratio. The former is the main stimulus for enhanced sirtuin - protein deacetylase SIRT1 activity; the latter activatesAMP-dependent protein kinase (AMPK). Both SIRT1 and AMPK exert their major metabolic activities such as fatty acid oxidation andblock of glycolysis and protein, nucleotide and fatty acid synthesis through the effector protein peroxisome proliferator activatedreceptor gamma 1 α coactivator (PGC-1α). PGC-1α cooperates with PPAR α and their activities might contribute to potentialanti-cancer effects of CRKD, which were reported for various brain tumors. Interplay between SIRT1, AMPK, PGC-1α and PPAR α seemsto be the basis of anti-tumor dietary approach which may effectively supplement chemotherapy, especially that it is cheap and safe.PMID: 21133850

ca-0804.pdf http://www.medicinacomplementar.com.br/convertido/ca-0804.htm

1 de 1 10/10/2011 16:39