Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract.

We previously provided evidence supporting the existence of a novel leptin-independent body weight homeostat ("the gravitostat") that senses body weight and then initiates a homeostatic feed-back regulation of body weight. We, herein, hypothesize that this feed-back regulation involves a CNS mechanism. To identify populations of neurones of importance for the putative feed-back signal induced by increased loading, high-fat diet-fed rats or mice were implanted intraperitoneally or subcutaneously with capsules weighing ∼15% (Load) or ∼2.5% (Control) of body weight. At 3-5 days after implantation, neuronal activation was assessed in different parts of the brain/brainstem by immunohistochemical detection of FosB. Implantation of weighted capsules, both subcutaneous and intraperitoneal, induced FosB in specific neurones in the medial nucleus of the solitary tract (mNTS), known to integrate information about the metabolic status of the body. These neurones also expressed tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbH), a pattern typical of norepinephrine neurones. In functional studies, we specifically ablated norepinephrine neurones in mNTS, which attenuated the feed-back regulation of increased load on body weight and food intake. In conclusion, increased load appears to reduce body weight and food intake via activation of norepinephrine neurones in the mNTS.