Ces3/Tgh(-/-) mice with deficient VLDL production exhibited attenuated plasma lipids and reduced tumor weight, demonstrating that tumor-induced hyperlipidemia supports tumor growth.
Tumor-induced hyperlipidemia promotes tumor growth by reprogramming hepatic lipoprotein homeostasis, a process that can be attenuated by inhibiting VLDL production.
The known link between obesity and cancer suggests an important interaction between the host lipid metabolism and tumorigenesis. Here, we used a syngeneic tumor graft model to demonstrate that tumor development influences the host lipid metabolism. BCR-Abl-transformed precursor B cell tumors induced hyperlipidemia by stimulating very low-density lipoprotein (VLDL) production and blunting VLDL and low-density lipoprotein (LDL) turnover. To assess whether tumor progression was dependent on tumor-induced hyperlipidemia, we utilized the VLDL production-deficient mouse model, carboxylesterase3/triacylglycerol hydrolase (Ces3/TGH) knockout mice. In Ces3/Tgh(-/-) tumor-bearing mice, plasma triglyceride and cholesterol levels were attenuated. Importantly tumor weight was reduced in Ces3/Tgh(-/-) mice. Mechanistically, reduced tumor growth in Ces3/Tgh(-/-) mice was attributed to reversal of tumor-induced PCSK9-mediated degradation of hepatic LDLR and decrease of LDL turnover. Our data demonstrate that tumor-induced hyperlipidemia encompasses a feed-forward loop that reprograms hepatic lipoprotein homeostasis in part by providing LDL cholesterol to support tumor growth.
Huang et al. (Fri,) conducted a other in Tumor-induced hyperlipidemia. Ces3/TGH knockout vs. Wild-type mice was evaluated on Tumor weight and plasma lipid levels. Ces3/Tgh(-/-) mice with deficient VLDL production exhibited attenuated plasma lipids and reduced tumor weight, demonstrating that tumor-induced hyperlipidemia supports tumor growth.