Doxorubicin treatment inhibits PPARγ and may induce lipotoxicity by mimicking a type 2 diabetes-like condition in rodent models

被引:72
作者
Arunachalam, Sankarganesh
Pichiah, P. B. Tirupathi [2 ]
Achiraman, Shanmugam [1 ]
机构
[1] Bharathidasan Univ, Dept Environm Biotechnol, Sch Environm Sci, Tiruchirappalli 620024, Tamil Nadu, India
[2] Chonbuk Natl Univ, Dept Food Sci & Human Nutr, Jeonju 561756, Jeonbuk, South Korea
关键词
Doxorubicin; PPAR gamma; Adipogenesis; Type; 2; diabetes; Adipose tissue inflammation; PROLIFERATOR-ACTIVATED RECEPTORS; INDUCED INSULIN-RESISTANCE; DIET-INDUCED OBESITY; ADIPOSE-TISSUE; FATTY-ACIDS; GLUCOSE-METABOLISM; GENE-EXPRESSION; ADRIAMYCIN; ALPHA; MICE;
D O I
10.1016/j.febslet.2012.11.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Doxorubicin-treated animals show elevated serum triglyceride and blood glucose levels. Adipocytes play an important role in buffering blood glucose and lipids. A raise in serum lipid level triggers adipogenesis in order to increase the lipid absorption capacity of adipose tissue. Doxorubicin inhibits adipogenesis through the down-regulation of PPAR gamma, a crucial component of the lipid metabolic pathway which controls the expression of glucose and fatty acid transporters. Doxorubicin-mediated down-regulation of PPAR gamma inhibits blood glucose and lipid clearance thereby causing hyperglycemia and hyperlipidemia resulting in lipotoxicity, glucotoxicity, inflammation and insulin resistance. Therefore we hypothesize that doxorubicin treatment could mimic a type 2 diabetic condition. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:105 / 110
页数:6
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