Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/93433
Type: Artigo
Title: Western diet modulates insulin signaling, C-jun N-terminal kinase activity, and insulin receptor substrate-1ser307 phosphorylation in a tissue-specific fashion
Title Alternative: 
Author: Prada, P.O.
Gasparetti, A.L.
Zecchin, H.G.
Hoer, N.F.
Hirata, A.E.
Torsoni, M.A.
Corezola do Amaral, M.E.
Ueno, M.
Boschero, A.C.
Saad, M.J.A.
Abstract: The mechanisms by which diet-induced obesity is associated with insulin resistance are not well established, and no study has until now integrated, in a temporal manner, functional insulin action data with insulin signaling in key insulin-sensitive tissues, including the hypothalamus. In this study, we evaluated the regulation off insulin sensitivity by hyperinsulinemic-euglycemic clamp procedures and insulin signaling, c-jun N-tenminal kinase (JNK) activation and insulin receptor substrate (IRS)-1ser307 phosphorylation in liver, muscle, adipose tissue, and hypothalamus, by immunoprecipitation and immunoblotting, in rats fed on a Western diet (WD) or control diet for 10 or 30 d. WD increased visceral adiposity, serum triacylglycerol, and insulin levels and reduced whole-body glucose use. After 10 d of WD (WB10) there was a decrease in IRS-1/phosphatidylinositol 3-kinase/protein kinase B pathway in hypothalamus and muscle, associated with an attenuation of the anorexigenic effect of insulin in the former and reduced glucose transport in the latter. In WD10, there was an increased glucose transport in adipose tissue in parallel to increased insulin signaling in this tissue. After 30 d of WD, insulin was less effective in suppressing hepatic glucose production, and this was associated with a decrease in insulin signaling in the liver. JNK activity and IRS-1 ser307 phosphorylation were higher in insulin-resistant tissues. In summary, the insulin resistance induced by WD is tissue specific and installs first in hypothalamus and muscle and later in liver, accompanied by activation of JNK and IRS-1ser307 phosphorylation. The impairment of the insulin signaling in these tissues, but not in adipose tissue, may lead to increased adiposity and insulin resistance in the WD rats.
The mechanisms by which diet-induced obesity is associated with insulin resistance are not well established, and no study has until now integrated, in a temporal manner, functional insulin action data with insulin signaling in key insulin-sensitive tissues, including the hypothalamus. In this study, we evaluated the regulation off insulin sensitivity by hyperinsulinemic-euglycemic clamp procedures and insulin signaling, c-jun N-tenminal kinase (JNK) activation and insulin receptor substrate (IRS)-1ser307 phosphorylation in liver, muscle, adipose tissue, and hypothalamus, by immunoprecipitation and immunoblotting, in rats fed on a Western diet (WD) or control diet for 10 or 30 d. WD increased visceral adiposity, serum triacylglycerol, and insulin levels and reduced whole-body glucose use. After 10 d of WD (WB10) there was a decrease in IRS-1/phosphatidylinositol 3-kinase/protein kinase B pathway in hypothalamus and muscle, associated with an attenuation of the anorexigenic effect of insulin in the former and reduced glucose transport in the latter. In WD10, there was an increased glucose transport in adipose tissue in parallel to increased insulin signaling in this tissue. After 30 d of WD, insulin was less effective in suppressing hepatic glucose production, and this was associated with a decrease in insulin signaling in the liver. JNK activity and IRS-1 ser307 phosphorylation were higher in insulin-resistant tissues. In summary, the insulin resistance induced by WD is tissue specific and installs first in hypothalamus and muscle and later in liver, accompanied by activation of JNK and IRS-1ser307 phosphorylation. The impairment of the insulin signaling in these tissues, but not in adipose tissue, may lead to increased adiposity and insulin resistance in the WD rats
Subject: Glicose
Insulina
Resistência à insulina
Country: Estados Unidos
Editor: Oxford University Press
Citation: Endocrinology. , v. 146, n. 3, p. 1576 - 1587, 2005.
Rights: fechado
Identifier DOI: 10.1210/en.2004-0767
Address: https://academic.oup.com/endo/article/146/3/1576/2501259
Date Issue: 2005
Appears in Collections:IB - Artigos e Outros Documentos
FCM - Artigos e Outros Documentos

Files in This Item:
File Description SizeFormat 
2-s2.0-20044364733.pdf945.56 kBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.