Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/200454
Type: Artigo de periódico
Title: Inhibition Of 72 Kda Inositol Polyphosphate 5-phosphatase E Improves Insulin Signal Transduction In Diet-induced Obesity.
Author: Bertelli, Daniela F
Coope, Andressa
Caricilli, Andrea M
Prada, Patricia O
Saad, Mario J
Velloso, Licio A
Araujo, Eliana P
Abstract: The 72 kDa inositol polyphosphate 5-phosphatase E (72k-5ptase) controls signal transduction through the catalytic dephosphorylation of the 5-position of membrane-bound phosphoinositides. The reduction of 72k-5ptase expression in the hypothalamus results in improved hypothalamic insulin signal transduction and reduction of food intake and body mass. Here, we evaluated the tissue distribution and the impact of obesity on the expression of 72k-5ptase in peripheral tissues of experimental animals. In addition, insulin signal transduction and action were determined in an animal model of obesity and insulin resistance treated with an antisense (AS) oligonucleotide that reduces 72k-5ptase expression. In lean Wistar rats, 72k-5ptase mRNA and protein are found in highest levels in heart, skeletal muscle, and white adipose tissue. In three distinct models of obesity, Wistar rats, Swiss mice fed on high-fat diet, and leptin-deficient ob/ob mice, the expression of 72k-5ptase is increased in skeletal muscle and adipose tissue. The treatment of obese Wistar rats with an anti-72k-5ptase AS oligonucleotide results in significant reduction of 72k-5ptase catalytic activity, which is accompanied by reduced food intake and body mass and improved insulin signal transduction and action as determined by immunoblotting and clamp studies respectively. 72k-5ptase expression is increased in obesity and its AS inhibition resulted in a significant improvement in insulin signal transduction and restoration of glucose homeostasis.
Subject: Adipose Tissue, White
Animals
Diet, High-fat
Disease Models, Animal
Insulin
Insulin Resistance
Leptin
Male
Mice
Mice, Obese
Muscle, Skeletal
Myocardium
Obesity
Oligoribonucleotides, Antisense
Phosphoric Monoester Hydrolases
Rats
Rats, Wistar
Signal Transduction
Rights: fechado
Identifier DOI: 10.1530/JOE-12-0562
Address: http://www.ncbi.nlm.nih.gov/pubmed/23349329
Date Issue: 2013
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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