Overexpression of hypothalamic TXNIP contributes to obesity and impaired blood glucose control.
New research suggests potential clinical applications of a hypothalamic cell protein for the treatment of obesity and type 2 diabetes. Studies in mouse models by the team at Einstein College of Medicine at Yeshiva University indicate that overexpression of thioredoxin-interacting protein (TXNIP) by hypothalamic nutrient-sensing cells as result of excess nutrient availability may directly contribute to the onset of obesity and the impaired control of blood sugar levels.
Working with mouse models of both obesity and type 2 diabetes, the team, led by Clémence Blouet, Ph.D., and Gary Schwartz, Ph.D., professor in the Dominick P. Purpura department of neuroscience at the Albert Einstein College of Medicine, found that an excess of nutrients leads to overproduction of TXNIP in nutrient-sensing nerve cells. Elevated TXNIP in effect directly contributed to obesity by decreasing energy expenditure in the form of decreased physical activity and reducing the rate at which fat is burned. Overabundance of hypothalamic TXNIP also impaired glucose tolerance and insulin sensitivity, two of the major features of diabetes, they report. Their findings are published in the Journal of Neuroscience in a paper titled “Nutrient-sensing hypothalamic TXNIP links nutrient excess to energy imbalance in mice.”
“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,” Dr. Schwartz claims. “Interventions that can suppress TXNIP production or selectively inactivate this protein might help in preventing weight gain and the obesity and diabetes that result from it.”