I love coconut. I love the nutty, sweet flavor in everything from candy and cakes to refreshing beverages and savory curries. But once, as I was cooking a coconut-based curry, I opened a spoiled can of coconut milk, and I immediately lost my appetite. There was nothing unusual about the visual appearance or texture of the coconut milk, but the smell was horrendous. I threw the can away – outside – and didn’t eat dinner.
Research has shown that our sense of smell has a large impact on our appetite. Many of us know this from experience – we get hungry when we walk into a bakery smelling of fresh bread and lose our appetite when we walk past a foul-smelling dumpster. However, the neuroscience of how smell is linked to appetite is not well understood.
The process of sensing smell is known as olfaction. Cells in the nasal cavity detect odor in the air we breathe in, then relay information about that odor via the olfactory bulb to the olfactory cortex. The olfactory cortex then signals to neurons in the brain that control our conscious perception of smell.
Appetite is controlled primarily by two types of neurons located in the arcuate nucleus of the hypothalamus region in the brain. Agouti-related peptide (AgRP) neurons stimulate appetite while pro-opiomelanocortin (POMC) neurons suppress it. Studies have shown that the smell and sight of food influence both AgRP and POMC neuron activity. The neural pathway that connects the olfactory cortex and these appetite neurons, however, has not been defined.
In a study recently published in PNAS, researchers in Dr. Linda Buck’s lab in the Basic Sciences Division investigated this pathway, utilizing a virus that travels retrograde through neuron synapses. They introduced the virus into either AgRP or POMC neurons in mice and tracked where in the brain the virus spread over the course of four days. Working backwards, they mapped out the neural connections between the olfactory cortex and the two types of appetite neurons.
The results showed that the signaling between the olfactory cortex and appetite neurons is indirect, with signals traveling through neurons in other brain areas before reaching the arcuate nucleus. And the pathways upstream of AgRP and POMC neurons are different. They originate from partially overlapping, but distinct regions within the olfactory cortex. This suggests that AgRP and POMC neurons each receive unique information.
The leading author of the study, Dr. Dawn Kuang, explained, “these findings raise new questions about how different olfactory cortical regions contribute to appetite regulation and whether they convey distinct types of sensory information — such as attraction or aversion — to appetite-controlling neurons. We would like to know whether appetizing food odors preferentially activate the AgRP-projecting olfactory cortical areas, while aversive or satiating odors activate POMC-projecting areas.”
The results also revealed that the vomeronasal amygdala, a brain region that transmits signals from detected social cues, signals to appetite neurons. Surprisingly, these signals are more directly upstream than signals communicating scent through the olfactory cortex. This unexpected finding raises questions of how social stimuli, such as pheromones or predator odors, may play an important part in driving appetite and eating behavior.
“Future research will aim to determine the specific roles of the upstream brain regions and neuronal populations in appetite regulation by olfactory cues and social cues,” indicated Dr. Kuang. “By dissecting these circuits and molecular pathways in greater detail, this work may also help identify new therapeutic targets for disorders of appetite and metabolism.”
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Members Drs. Manu Setty and Linda Buck contributed to this research.
The spotlighted research was funded by the Howard Hughes Medical Institute, the National Institutes of Health, and the Millen Literary Trust.
Kuang D, Hanchate NK, Lee C-Y, Heck A, Ye X, Erdenebileg M, Mehta C, Hassan MM, Setty M, Buck LB. 2026. Olfactory inputs to appetite neurons in the hypothalamus. PNAS. doi: 10.1073/pnas.2524926123
Science Spotlight writer Ashley Person is a PhD candidate in the Cohn lab in the Vaccine and Infectious Disease Division at Fred Hutch. She studies how HIV-infected cells persist over time in people living with HIV on long term treatment.