Elevated lipolysis in adipose tissue by doxorubicin via PPARα activation associated with hepatic steatosis and insulin resistance.Eur J Pharmacol 2019; 843:162-176EJ
Adipose dysfunction is tightly associated with hepatic insulin resistance and steatosis condition. Doxorubicin would disturb the lipid metabolism both in adipose and liver. Here we projected that doxorubicin would impede lipogenesis and elevated lipolysis in adipose tissue would elevate the circulatory lipid profile and leads to insulin resistance. Further exacerbated lipid profile in circulation would impair the lipid metabolism in hepatic tissue which leads to fatty liver condition and consequently related disease during doxorubicin treatment. Doxorubicin impairs the lipogenesis through PPARγ and augments lipolysis and fatty acid oxidation through ATGL and PPARα in adipose tissue. Increased fatty acid level by adipose tissue in circulation would translocate into the liver and dysregulates AHR, PXR, PPARγ, ATGL and Apo B,which further develop insulin resistance and hepatic steatosis condition. The findings add to the mechanistic role of association between adipose tissue dysfunction and hepatic dysfunction.