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

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.

► Doxorubicin down-regulates PPARγ, may subsequently affect the expression of GLUT4 & FAT/CD36.
► Reduction of glucose and fatty acid transporters would cause hyperglycemia and hyperlipidemia.
► Free fatty acids induced inflammation of adipose tissue leads to insulin resistance.
► Inflamed adipose tissue confers to type 2 diabetes like condition in doxorubicin treated animals.