To Curb Appetite, Study its Very Origins
In an age when the disconnect between overeating and knowledge of its negative consequences is arguably at an all-time high, welcome new NIH-funded research out of Beth Israel Deaconess Medical Center (BIDMC), a research affiliate of Harvard Medical School, has discovered the involvement of a new cluster of neurons in the regulation of hunger. The research moves us closer to a complete picture of appetite regulation, and some would say not a moment too soon.
Hunger is a hard-wired state that motivates specific action for survival: eating. Neuroscience is continually trying to better understand its roots and inner workings, one wants to believe as much as in the interest of public health as in pure scientific discovery or of profit. The ultimate goal is to untangle the complicated jumble of neurocircuits in the brain that underlie hunger to create a kind of “wiring diagram” to explain its origins and control its darker urges.
The new findings add an important extension to our understanding of what drives appetite. We previously have understood that an amino-acid compound called Agouti-related peptide (AgRP) gets expressed in a cluster of neurons at the base of the hypothalamus that are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they induce intense hunger. Similarly, chemogenetic inhibition of these AgRP neurons decreases feeding.
Excitatory input to AgRP neurons is important in their activation. Despite the important role of this input, its source has been unknown. But now, using cell-specific neuron-mapping techniques with mice, the BIDMC group discovered a strong excitement-producing drive that emanates from an area of the hypothalamus not previously thought to be involved in the hunger response—to the contrary, the brain region in question has long been associated with causing feelings of fullness. Furthermore, in sated mice stimulation of a newly recognized subset of neurons expressing a hormone known as TRH (for thyrotropin-releasing hormone) induced intense feeding. Inhibition of these neurons, which also activate pituitary adenylate cyclase, decreased feeding in calorically deficient mice. The discovery further advises against referring to this latter group of mice as hungry, as caloric-deficiency and hunger are really quite different.
“Afferent” neurons refer to those that carry nerve impulses toward, as opposed to away from, the central nervous system. Hunger is an intensely motivational state and the complicated picture of how it is regulated has been made more finely detailed again with the exciting discovery of these specific afferent neurons that are so directly involved with triggering it.
As the BIDMC team writes, “While the function of eating is to nourish the body, this is not what actually compels us to seek out food. Instead, it is hunger, with its stomach-growling sensations and gnawing pangs that propels us to the refrigerator – or the deli or the vending machine. Although hunger is essential for survival, abnormal hunger can lead to obesity and eating disorders, widespread problems now reaching near-epidemic proportions around the world.” When hunger and caloric deficiency can be completely separated, we will potentially have a very real solution to many of the health problems associated with overweight and obesity that now so devastate the more affluent nations among us.