Which neural circuits are involved in metabolism?

Metabolism and body weight are regulated by a complex network of nerve cells and hormones that control appetite, food intake and energy expenditure.

The hunger and satiety neurons

One of the most important areas of the brain involved in metabolism is the hypothalamus. It contains several groups of nerve cells that send signals about the availability of and need for nutrients. One important group of nerve cells is called AgRP neurons. They are found exclusively in the hypothalamus and regulate appetite. When an organism has not eaten for a long time, AgRP neurons are activated and release certain messengers (neurotransmitters) called AgRP, GABA and NPY. The result is an increase in hunger, which ultimately increases food intake. At the same time, the body's energy expenditure is reduced. In contrast, POMC neurons are also located in the hypothalamus. These neurons are necessary for the feeling of satiety and inhibit appetite while increasing the body's energy expenditure [Brüning & Fenselau, 2023].

Hormonal regulation of appetite: the role of leptin, ghrelin and insulin

The activity of AgRP and POMC neurons is significantly influenced by the release of different hormones. These hormones usually have opposite effects on hunger and satiety neurons.

When an organism has stored enough energy and has increased fat stores, leptin is released from the body's fat cells into the blood. The released leptin binds to the leptin receptor, which is leptin's docking station on cells. This endocrine communication inhibits the hunger neurons (AgRP neurons) and activates the satiety neurons (POMC neurons). Leptin therefore inhibits food intake while increasing energy expenditure [Timper & Brüning, 2017].

Ghrelin, a hormone mainly produced in the stomach [Kojima et al., 1999], has exactly the opposite effect on the two groups of neurons. While it increases the activity of the hunger neurons, it inhibits the satiety hormones [Korbonits et al, 2004]. Thus, an increase in ghrelin levels in the blood, triggered by an empty stomach, has an appetising effect.

Insulin from the pancreas can also affect an organism's metabolism by altering eating behaviour. Experiments on mice have shown that a lack of insulin receptors can cause mice to eat more and, in the long term, lead to insulin resistance and obesity [Brüning et al., 2000].

Direct and indirect interactions

The interconnection between AgRP and POMC neurons in the brain plays a crucial role in the regulation of food intake. The two sets of neurons interact to maintain the balance between hunger and satiety. Activation of the hunger neurons (AgRP neurons) by a state of hunger directly inhibits the downstream satiety neurons through the release of the neurotransmitters AgRP, NPY and GABA. Conversely, activation of satiety neurons (POMC neurons) after food intake leads to the release of the neurotransmitter αMSH, which in turn overrides the inhibition of downstream satiety neurons [Vicent et al., 2018]. This overrides the inhibition by the AgRP neurons.

The hormones leptin, insulin and ghrelin can also act both directly and indirectly on hunger and satiety neurons. Directly, by binding to receptors on the neurons themselves and influencing their activation. Indirectly, by activating other neurons, called interneurons, which in turn regulate the activity of the hunger and satiety neurons. For example, receptors for leptin and insulin are formed by only a few POMC neurons [Williams et al., 2010], so the hormones mainly regulate the activity of satiety and hunger neurons indirectly by binding to interneurons [Cowley et al., 2001; Berglund et al., 2012].

What is metabolism?

What is overweight? What is obesity?

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