Humoral Inputs Humoral signals include meal control signals from the gastrointestinal tract, blood nutrient levels that are used by brain circuits as measures of the metabolic status of the body (Sanchez-Lasheras, K?nner, & Br��ning, Y27632 2010), and adiposity signals from the WAT (the body energy stores). Meal control signals include gastric and intestinal wall distension and hormones released from enteroendocrine cells (Castaneda, Tong, Datta, Culler, & Tsch?p, 2010; Chaudhri, Salem, Murphy, & Bloom, 2008). The former is recorded by stretch receptors in the digestive system and is transmitted through the vagus and sympathetic nerves to the brain stem (Cummings & Overduin, 2007).

Enteroendocrine cells associated with the gastrointestinal tract are modulated by neuronal or hormonal signals, sense nutrient levels and taste of the gastrointestinal content through a wide array of G-protein coupled receptors (Geraedts, Troost, & Saris, 2011), and produce short-lived hormones that promote appetite (ghrelin, from the gastric fundus and, to a lower extent, small intestine) or satiation (the principal hormones are cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and serotonin (5HT) from small intestine). Note that in this context, satiation refers to the processes involved in meal termination whereas satiety refers to the postprandial absence of hunger, which contributes to the determination of the interval between meals. Overall, release of these hormones depends on meal content and is broadly related to energy content but also depends on meal quality (Cummings & Overduin, 2007; Young, 2011).

These hormones can act directly on receptors expressed by hypothalamic and/or brain stem neurons and/or indirectly on receptors expressed on vagus nerve terminals that project to the NTS. Acute or chronic nicotine treatment can change RNA expression and plasma levels of several enteroendocrine peptides (Chowdhury, Hosotani, Chang, & Rayford, 1990; Chowdhury, Hosotani, & Rayford, 1989; Gomez et al., 1996; Wong & Ogle, 1995). The existence of direct effects on enteroendocrine cells has not been extensively investigated. nAChRs stimulate 5HT release from enterochromaffin cells (Racke, Reimann, Schw?rer, & Kilbinger, 1996), whereas no evidence for release of histamine or gastrin was obtained (Brenna et al., 1993; Matsuno, Matsui, Iwasaki, & Arakawa, 1997).

Localization of nAChR immunoreactivity in the bowel mucosa showed positivity in a subset of enterochromaffin cells, and no signal in any other kind of enteroendocrine or nonendocrine cell (Kirchgessner & Liu, AV-951 1998). Overall, it is likely that nicotine-induced alterations of enteroendocrine hormones are largely indirect, mediated by the autonomic and enteric nervous systems and changes in food intake and enteric motility. Adiposity signals are tonically released in proportion to total body fat, the primary body energy stores.