Appetite Neurobiology

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Comorbidities of obesity

type 2 diabetes, hypertension, cardiovascular disease, abnormal blood lipid levels, sleep apnea, fatty liver disease, osteoarthritis, certain cancers, and increased risk of depression or anxiety.

One of the most fundamental influences on appetite

presence of food in the alimentary canal

Distension

stretching or expansion of the intestinal wall when food or other material fills the lumen.

When the intestinal wall is stretched, such as by the presence of food, the ion channels are pulled open, allowing ions to enter the neuron. This alters the neuron’s membrane potential and increases the frequency at which it fires action potentials.​

absence of distension

small intestine is empty and its wall is relaxed, the stretch receptors are not activated. The ion channels remain closed, preventing ion flow across the membrane, and the associated neuron remains at rest, and the frequency of action potentials decreases.​

ARC

arcuate nucleus, or ARC, acting as the main integration site.

The ARC contains two groups of neurons that work in opposite ways: POMC, and CART, neurons, which reduce appetite and promote satiety, and NPY, AgRP, neurons, which increase food intake.​

POMC

pro-opiomelanocortin

reduce appetite and promote satiety

CART

cocaine- and amphetamine-regulated transcript

reduce appetite and promote satiety

NPY

neuropeptide Y

increase food intake.

AgRP

agouti-related peptide

increase food intake.

PVN

paraventricular nucleus

POMC/CART AND NPY/AgRP

DMN

dorsomedial nucleus

POMC/CART

VMH

ventromedial nucleus

POMC/CART

LHA

lateral hypothalmic area

NPY/AgRP

reward pathway

Some people overeat because the normal signals that control appetite and satiety become disrupted. This can happen when the brain’s reward pathways override signals from the hypothalamus and brainstem that indicate fullness, causing eating to continue even when energy needs are met. In some individuals, the sensitivity of neurons in the arcuate nucleus or the response to gut hormones like CCK and GLP-1 is reduced, so the feeling of satiety occurs later or is weaker. Emotional stress, highly palatable foods rich in sugar and fat, and learned eating behaviors can also exaggerate hunger signals and make it harder to stop eating when full.​

how signals from the intestines influence appetite regulation through their effects on the arcuate nucleus.

When food enters the small intestine, the wall stretches, creating distension that activates sensory pathways leading to the nucleus of the solitary tract (NTS) in the brainstem.

cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1)

The intestines release hormones such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) in response to nutrients, particularly fats and carbohydrates. These hormones act on receptors that send information to the NTS, which then communicates with the hypothalamus, including the ARC. These hormones, among others, also get into circulation, and can affect the hypothalamus via that route. Signals from the NTS activate the POMC/CART neurons in the hypothalamus, which suppress appetite, and simultaneously inhibit the NPY/AgRP neurons, which normally stimulate hunger.​​

Through this coordination between the intestines, NTS, and hypothalamus, the brain receives information that food has entered the digestive system, leading to reduced hunger and a sense of fullness after eating. This is called meal-ending satiety.