Einstein researchers have found a molecule in the brain that may contribute to obesity and one of its major complications – type 2 diabetes.
Nerve cells in the brain”s hypothalamus detect nutrients and hormones circulating in the blood and then coordinate a complex series of behavioral and physiological responses to maintain a balance between calories eaten and calories burned.
Obesity and diabetes can result when this regulatory mechanism goes awry.
Now, a research by postdoctoral fellow Clemence Blouet and Prof Gary Schwartz at the Albert Einstein College of Medicine of Yeshiva University has revealed a molecule in the brain that may contribute to those health problems.
Their study on mouse models has shown that excess nutrient availability leads to an overabundance of a protein found in nutrient-sensing nerve cells of the hypothalamus.
They concluded that increased levels of this protein, known as thioredoxin-interacting protein, or TXNIP, contribute to the onset of obesity and the impaired control of blood sugar levels that characterizes type 2 diabetes.
“Our study indicates that TXNIP in hypothalamic nerve cells provides a crucial link between brain nutrient sensing and the increases in body weight and fat mass that lead to obesity and diabetes,” said Schwartz.
“Hyperglycemia—pathologically elevated glucose levels—causes an excess of TXNIP in hypothalamic neurons, which in turn may contribute in several ways to a breakdown in energy homeostasis—the balance between calories taken in and calories burned.
“For example, we”ve found that elevated TXNIP in nerve cells contributes to obesity by decreasing energy expenditure, as evidenced by decreased physical activity, and by reducing the rate at which fat is burned to produce energy. In addition to increasing fat mass, hypothalamic TXNIP overabundance also impairs glucose tolerance and insulin sensitivity—two of the hallmarks of diabetes,” said Schwartz.
Their findings were published in the April 20 online edition of the Journal of Neuroscience.