Gut-to-brain signals in feeding control

Abstract

Interoceptive signals from gut and adipose tissue and sensory cues from the environment are integrated by hubs in the brain to regulate feeding behavior and maintain homeostatic control of body weight. In vivo neural recordings have revealed that these signals control the activity of multiple layers of hunger neurons and eating is not only the result of feedback correction to a set point, but can also be under the influence of anticipatory regulations. A series of recent technical developments have revealed how peripheral and sensory signals, in particular, from the gut are conveyed to the brain to integrate neural circuits. Here, we describe the mechanisms involved in gastrointestinal stimulation by nutrients and how these signals act on the hindbrain to generate motivated behaviors. We also consider the organization of multidirectional intra- and extrahypothalamic circuits and how this has created a framework for understanding neural control of feeding.

Keywords: feeding; gut-to-brain; hypothalamus.

Figure 1.

Vagal afferent neurons. The gastrointestinal tract is densely innervated by the vagus nerve and its mucosal endings acts as chemosensory terminals detecting nutrients and hormones, whereas the IGLEs are anatomically concentrated in muscle layers and detect gastrointestinal stretch. The cell bodies of the afferent fibers are located in the nodose ganglia and the signals from their terminals are relayed to the NTS. The PBN, in turn, receives ascending inputs from the NTS and coordinates meal termination. IGLEs, intraganglionic laminar endings; NTS, nucleus tractus solitarius; PBN, parabrachial nucleus.

Figure 2.

Novel ARC and PVH neurons. PNOC-expressing neurons are activated by short-term HFD feeding and, in concert with AgRP neurons, inhibit POMC neurons through GABAergic projections. Recent studies suggest a distinct GABAergic neuronal population as the primary effector of leptin signaling in the ARC. The ARC neurons project to and target PVH neurons to control feeding. GLP1R, MC4R, and PDYN are expressed in different neurons in PVH and their activation induce satiety through different efferent circuitry in PBN. AgRP, agouti-related peptide; ARC, arcuate nucleus; GABA, gamma-aminobutyric acid; GLP1R, glucagon-like peptide-1 receptor; MC4R, melanocortin-4 receptor; PBN, parabrachial nucleus; PDYN, prodynorphin; PNOC, prepronociceptin; POMC, pro-opiomelanocortin; PVH, paraventricular nucleus; 3V, third ventricle.