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

FEBS Lett. 2013 Jan 16;587(2):105-10. doi: 10.1016/j.febslet.2012.11.019. Epub 2012 Dec 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / chemically induced*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Models, Animal
  • Doxorubicin / toxicity*
  • Humans
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Insulin Resistance
  • Lipids / blood*
  • Metabolic Networks and Pathways / drug effects
  • Mice
  • Models, Biological
  • PPAR gamma / antagonists & inhibitors*

Substances

  • Blood Glucose
  • Lipids
  • PPAR gamma
  • Doxorubicin