UCP family (UCP1-3 genes) is widely known to be highly expressed in brown fat/adipose tissue and contributes to dissipating energy as heat instead of generating ATP from the oxidation of free fatty acids. In particular, UCP-1 is stimulated by the adrenergic neurons in the sympathetic nervous system, mediated by the β3adrenoceptor. There has been several reports that at the late stage of cancer patients, the loss of body weight and skeletal muscle known as “cachexia,” is deeply related to the up-regulation of UCP genes in the cancer cells (Cancer Res May 1, 2000 60;2405.). Intriguingly, it has recently been uncovered that UCP-1 up-regulation in the tumor stroma contributes to the interaction cancer cells with the tumor microenvironment composed of cancer-associated fibroblasts. CAFs highly express of UCP-1 in stromal fibroblasts increases β-oxidation of free fatty acids, ketone body production and the release of ATP-rich vesicles, which “fuels” tumor development by providing high-energy nutrients in a paracrine fashion to epithelial cancer cells (Cell Cycle. 2013 Jan 1;12(1):172-82. ). This seems to be paradoxical as compared with the well-recognized function of heat production by UCP family, however, I believe emerging concept of mitochondrial UCP-1 is partially responsible for the phenomenon in cancer metabolism which cannot be simply explained by “Warburg effect.”

Mr Yoshida is there any studies or articles showing upregulation of Uncoupling proteins in chronic inflammatory states. That would be the most powerful logic for role of chronic inflammatory states in cancer. Because uncoupling of ETS and glycolysis has been shown to promote cancer..

Uncoupling of glycolysis from oxidative phosphorylation makes sense because it allows glycolysis to proceed uninhabited...thus is explained by reports of upregulated Warburg effect in cancer and also of upregulated uncoupling proteins in cancer 

Mr Yoshida kindly have look at the schema.May this may ....?

https://www.researchgate.net/publication/274712018_Linking_chronic_inflammation_and_warburg_effect

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