Integration of Satiety Signals by the Central Nervous System

Abstract

Individual meals are products of a complex interaction of signals related to both short-term and long-term availability of energy stores. In addition to maintaining the metabolic demands of the individual in the short term, levels of energy intake must also maintain and defend body weight over longer periods. To accomplish this, satiety pathways are regulated by a sophisticated network of endocrine and neuroendocrine pathways. Higher brain centers modulate meal-size through descending inputs to caudal brainstem regions responsible for the motor pattern generators associated with ingestion. Gastric and intestinal signals interact with central nervous system pathways to terminate food intake. These inputs can be modified as a function of internal metabolic signals, external environmental influences, and learning to regulate meal-size.

Sensory Neurons that Detect Stretch and Nutrients in the Digestive System

“…Ingested nutrients activate enteroendocrine cells, sparsely distributed sentinel cells in the intestinal epithelium. Enteroendocrine cells respond to nutrients by releasing a myriad of gut hormones, including serotonin, glucagon-like peptide 1 (GLP1), cholecystokinin, peptide YY, and others (Chambers et al, 2013). Detection of different nutrients, perhaps through taste receptors (Jang et al, 2007), may evoke differential hormone secretion.…”

“…In some electrophysiological studies, each of these gut hormones reportedly activates lumen-proximal or nutrient-responsive vagal afferents (Blackshaw and Grundy, 1990; Zhu et al, 2001), and in other studies, the same gut hormones reportedly activate mechanoreceptors (Mazda et al, 2004; Schwartz et al, 1991). Different studies also claimed important roles for each hormone in various nutrient-evoked physiological responses (Chambers et al, 2013). A limitation of in vivo pharmacology is that injection of CCK and serotonin causes indirect responses, such as changes in gastrointestinal motility and tone.…”

Stereotyped responses of Drosophila peptidergic neuronal ensemble depend on downstream neuromodulators

“…The influence of neuropeptides can be profound and underlies the expression of entire behavioral states, such as hunger and satiation (Atasoy et al, 2012; Chambers et al, 2013; Gao and Horvath, 2007), pair bonding and stress (Lieberwirth and Wang, 2014; Neumann and Landgraf, 2012), and arousal and attention (Li et al, 2016), and can involve many brain regions in addition to sensory and physiological inputs. How these actions are effected is poorly understood because neuropeptides can be broadly released within the CNS and exert combinatorial and non-linear effects (Brezina, 2010).…”

Intestine-specific Deletion of Acyl-CoA:Monoacylglycerol Acyltransferase (MGAT) 2 Protects Mice from Diet-induced Obesity and Glucose Intolerance

“…These intestinal signals can in turn regulate food intake and coordinate metabolism, preparing the rest of the body for efficient use and storage of incoming nutrients (1)(2)(3). Acyl-CoA: monoacylglycerol acyltransferase (MGAT) 3 in the intestine is thought to be important for the absorption of dietary fat (4,5).…”