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Cell Signaling Pathway Implicated in Energy Balance

Pathway is abnormally activated in overfed mice

FRIDAY, Oct. 3 (HealthDay News) -- An inflammatory signaling pathway in the brain's energy regulation headquarters is abnormally activated in overfed mice, and blocking this pathway protects against obesity and diabetes, according to a study in the Oct. 3 issue of Cell.

Xiaoqing Zhang, Ph.D., from the University of Wisconsin-Madison, and colleagues studied changes in the IKKβ/NF-κB inflammatory signaling pathway in the hypothalamus in the brain, the "headquarters" for maintaining energy homeostasis, in response to overnutrition. Overnutrition had previously been shown to activate inflammatory pathways in peripheral metabolic tissues, they note, and blocking IKKβ is effective against obesity-induced type 2 diabetes.

The researchers found that this pathway was activated in the hypothalamus of mice fed a high-fat diet. Abnormal activation of this pathway blocked the signaling and actions of central insulin and leptin, hormones involved in blood sugar regulation and appetite control, respectively, which previous studies had shown was sufficient to promote obesity and type 2 diabetes. Suppression of this pathway protected against obesity and glucose intolerance, the authors report.

"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 and colleagues conclude.

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