When people are obese, their liver becomes inflamed, which can lead to cancer. This involves immune cells called macrophages that cause liver inflammation and cancer development. Recently, scientists found that liver nerves in obese individuals become disorganized and degenerate. New 3D imaging techniques show hepatic nerves are important in liver diseases caused by obesity. Studies in mice have shown that nerve fibers in the liver change as the disease worsens, similar to what is seen in humans. The liver's immune system includes various immune cells, which help keep the liver healthy by responding to damage. There seems to be a close relationship between these immune cells and the liver’s ...
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When people are obese, their liver becomes inflamed, which can lead to cancer. This involves immune cells called macrophages that cause liver inflammation and cancer development. Recently, scientists found that liver nerves in obese individuals become disorganized and degenerate. New 3D imaging techniques show hepatic nerves are important in liver diseases caused by obesity. Studies in mice have shown that nerve fibers in the liver change as the disease worsens, similar to what is seen in humans. The liver's immune system includes various immune cells, which help keep the liver healthy by responding to damage. There seems to be a close relationship between these immune cells and the liver’s nerves, suggesting they might communicate through specific receptors. In our preliminary study using mice fed a western diet (mimicking human obesity), a specific receptor on macrophages called ADRB2 (beta-2 adrenergic receptor) was found to protect against liver disease. Mice lacking this receptor developed tumors more often than normal mice. The production of a molecule called IL-10, which has anti-inflammatory effects, depends on signals involving this receptor. We believe that signals from sympathetic nerves help maintain liver health by promoting IL-10 production, protecting against inflammation and cancer. However, obesity reduces these nerve signals and IL-10 levels, leading to chronic inflammation and cancer. To explore this further, we aim to study the role of ADRB2 in obesity-induced liver cancer. This research is important because, despite the documented nerve loss in obesity, we don’t know whether and how nerve loss regulates liver inflammation and cancer. Our project aims to uncover how nerve and immune cell interactions in the liver contribute to obesity-induced cancer. We will also test if beta-2 adrenergic receptor agonists (e.g. salbutamol) could be utilized as a novel preventive and/or therapeutic intervention strategy for obesity-induced HCC.
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