Dynamics of Gut-Brain Communication Underlying Hunger

Abstract

Summary Communication between the gut and brain is critical for homeostasis, but how this communication is represented in the dynamics of feeding circuits is unknown. Here we describe nutritional regulation of key neurons that control hunger in vivo. We show that intragastric nutrient infusion rapidly and durably inhibits hunger-promoting AgRP neurons in awake, behaving mice. This inhibition is proportional to the number of calories infused but surprisingly independent of macronutrient identity or nutritional state. We show that three gastrointestinal signals – serotonin, CCK, and PYY – are necessary or sufficient for these effects. In contrast, the hormone leptin has no acute effect on dynamics of these circuits or their sensory regulation, but instead induces a slow modulation that develops over hours and is required for inhibition of feeding. These findings reveal how layers of visceral signals operating on distinct timescales converge on hypothalamic feeding circuits to generate a central representation of energy balance.

Advances in the physiology of gastric emptying

“…This inhibition is proportional to the number of calories but independent of the type of food and is mediated by CCK, peptide YY, and 5‐hydroxytryptamine (5HT). Leptin induces a slow modulation that develops over hours and is required for the inhibition of feeding …”

“…Leptin induces a slow modulation that develops over hours and is required for the inhibition of feeding. 104…”

Hypothalamic Neurons that Regulate Feeding Can Influence Sleep/Wake States Based on Homeostatic Need

“…The activity of arcuate neurons that express agouti-related protein (AgRP), neuropeptide Y (NPY), and γ-amino-butyric acid (GABA) (commonly referred to as “AgRP neurons”) increases during food deprivation [9-12]. These neurons are activated by the orexigenic hormones ghrelin [13-16] and asprosin [17], and are inhibited by the anorexigenic hormones insulin and leptin [18]. Optogenetic or chemogenetic stimulation of AgRP neurons increases food-seeking behavior in mice [19, 20].…”

A gut sensor for sugar preference

“…As early as 1952, it was known that animals prefer the side of a T-maze if rewarded by nutrients delivered directly into the stomach. 1 Although the responses depend on the nutrient’s caloric value, 7,8,11 how this value is signaled by the gut epithelium to drive preference is unknown. Of all macronutrients, sugars and available analogs have the most defined sensory properties.…”

“…Such preference depends on the sugar entering the intestine. 1–4 Although the brain is aware of the stimulus within seconds, 5–8 how the gut discerns the caloric sugar to guide choice is unknown. Recently, we discovered an intestinal transducer, known as the neuropod cell.…”