A study by a team at Okinawa Institute of Science and Technology Graduate University revealed that a protein called "XRN1" is involved in the regulation of appetite and obesity.
XRN1 is a protein that controls the final stages of mRNA degradation and plays an important role in gene activity.In this study, we found that deficiency of XRN1 in the forebrain of mice leads to increased appetite and obesity.
The XRN1-deficient mice showed a rapid increase in appetite, such as a daily increase in food intake about twice that of control mice.It was found that the cause of this was that XRN1-deficient mice showed resistance to leptin, a hormone that suppresses appetite, and even high concentrations of leptin, which should not be appetite in normal mice, were ineffective.
In addition, XRN1-deficient mice also showed resistance to insulin, which is a hormone that lowers blood glucose levels, and blood glucose levels and blood insulin levels increased significantly with aging.
There was no overall difference in energy expenditure between XRN1-deficient and control mice, but surprisingly, control mice can switch their energy sources between carbohydrate and fat during the night and during the day. In contrast, XRN1-deficient mice used carbohydrates as their main energy source day and night, and were unable to consume fat effectively.
In the hypothalamus of XRN1-deficient mice, abnormal activation of the nerve (AgRP neurons) producing the agouti-related peptide (AgRP), which is a powerful appetite-promoting substance, was observed. The researchers speculate that some mechanism of XRN1 deficiency may increase the activity of AgRP neurons and abolish leptin signals, which induces binge eating in mice.
In the future, we aim to elucidate the complete mechanism of how XRN1 acts in the brain and is involved in appetite regulation.
Paper information:[IScience] Neuronal XRN1 is required for maintenance of whole-body metabolic homeostasis
