Obesity leads to the release of cytokines into the bloodstream which impact the metabolism of breast cancer cells, making them aggressive to treatment.
Severe overweight can lead to various health impairments. Besides inducing cardiovascular diseases, obesity for example also promotes the development of cancer and metastases.
ACC1 acetyl-CoA-carboxylase 1, a central component of fatty acid synthesis. ACC1 mediates the chemical addition of carbon dioxide to acetyl-CoA, which results in malonyl-CoA. This reaction is the first and speed determining step in the fatty acid synthesis of all living organisms.
ACC1 enzymes is a key component of fatty acid synthesis, its function is impaired by the cytokines leptin and TGF-β. The levels of these cytokines are increased particularly in the blood of severely overweight people.
Fatty acid precursors promote metastasis. The inhibition of ACC1 leads to the accumulation of the fatty acid precursor acetyl-CoA. This precursor is transferred to certain gene switches that in turn increase the metastatic capacity of cancer cells by activating a specific gene program.
Scientists used human tissue from breast cancer metastases to show that ACC1 was less active. When the scientists blocked the unknown signaling pathway with an antibody directed against the leptin receptor, this led to a significantly reduced metastatic spread of breast cancer tumors in an experimental model.
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