Researchers have identified a protein in the hypothalamus that is “switched on” by overeating, thus triggering inflammation and affecting hormones which play a key role in energy regulation.
 
Dr Xiaoqing Zhang and colleagues from the University of Wisconsin and the University of California found that IKKβ/NF-κB normally exists in an inactive form. While inactive its key role is to inhibit the activity of the inflammatory protein NF-κB. However, studies on mice revealed that chronic over-nutrition appears to activate IKKβ/NF-κB, which triggers an inflammatory response, and leads to chronic metabolic inflammation.

Further studies in mice showed that once IKKβ/NF-κB had been switched on by over-nutrition  the mice started eating even more food, thus suggesting that the protein also plays a role in a pathway involving the regulation of food intake. Indeed, further investigations revealed that activated IKKβ/NF-κB led the mice to become resistant to insulin and the appetite-suppressing hormone leptin.

The researchers conclude: "Our results show that the hypothalamic IKKβ/NF-κB program is a general neural mechanism for energy imbalance underlying obesity and suggest that suppressing hypothalamic IKKβ/NF-κB may represent a strategy to combat obesity and related diseases.”

Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKβ/NF-κB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008;135:61-73.