Premium
Doxorubicin treatment inhibits PPARγ and may induce lipotoxicity by mimicking a type 2 diabetes‐like condition in rodent models
Author(s) -
Arunachalam Sankarganesh,
Tirupathi Pichiah P.B.,
Achiraman Shanmugam
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.11.019
Subject(s) - lipotoxicity , endocrinology , adipogenesis , medicine , doxorubicin , insulin resistance , adipose tissue , triglyceride , type 2 diabetes , hyperlipidemia , peroxisome proliferator activated receptor , inflammation , chemistry , glucose uptake , glucose homeostasis , insulin , diabetes mellitus , biology , cholesterol , receptor , chemotherapy
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 PPARγ, a crucial component of the lipid metabolic pathway which controls the expression of glucose and fatty acid transporters. Doxorubicin‐mediated down‐regulation of PPARγ 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.