Sleep deprivation causes the olfactory system to go into overdrive


When you’re sleep deprived, you tend to reach for doughnuts, fries and pizza.

A new Northwestern Medicine study has figured out why you crave more calorie-dense, high-fat foods after a sleepless night — and how to help thwart those unhealthy choices.

Blame it on your nose – or olfactory system — which is affected in two ways by sleep deprivation, according to the study.

First, it goes into hyperdrive, sharpening the food odors for the brain so it can better differentiate between food and non-food odors.

But then there is a breakdown in the communication with other brain areas that receive food signals. And with that, decisions about what to eat change.

“When you’re sleep deprived, these brain areas may not be getting enough information, and you’re overcompensating by choosing food with a richer energy signal,” said senior author Thorsten Kahnt, assistant professor of neurology at Northwestern University Feinberg School of Medicine.

“But it may also be that these other areas fail to keep tabs on the sharpened signals in the olfactory cortex. That could also lead to choosing doughnuts and potato chips,” Kahnt added.

The paper was published Oct. 8 in eLife.

Past research shows sleep deprivation increases certain endocannabinoids, which are naturally produced by the body and are important for feeding behavior and how the brain responds to odors, including food smells.

“We put all this together and asked if changes in food intake after sleep deprivation are related to how the brain responds to food odors, and whether this is due to changes in endocannabinoids,” Kahnt said.

“What makes our brain respond differently that makes us eat differently?”

He and colleagues investigated that question in a two-part experiment with 29 men and women, ages 18 to 40.

Study participants were divided into two groups. One got a normal night’s sleep, then four weeks later, were only allowed to sleep for four hours.

The experience was reversed for the second group.

The day after each night (good sleep and deprived sleep), scientists served participants a controlled menu for breakfast, lunch and dinner, but then also offered them a buffet of snacks. Scientists measured how much and what they ate.

“We found participants changed their food choices,” Kahnt said. “After being sleep deprived, they ate food with higher energy density (more calories per gram) like doughnuts, chocolate chip cookies and potato chips.”

Researchers also measured the participants’ blood levels of two endocannabinoid compounds — 2AG and 2OG. One of the compounds, 2-OG, was elevated after the night of sleep deprivation and this increase was related to changes in food selection.

In addition, scientists put subjects in an fMRI scanner before the buffet.

They then presented them with a number of different food odors and non-food control odors while they observed the piriform cortex, the first cortical brain region that receives input from the nose.

They observed that activity in the piriform cortex differed more between food and non-food odors when subjects were sleep deprived.

After sleepless night, your ‘tired’ nose fails to talk to brain regions directing food choices.

The piriform cortex normally sends information to another brain area, the insular cortex. The insula receives signals that are important for food intake, like smell and taste, and how much food is in the stomach.

But the insula of a sleep-deprived subject showed reduced connectivity (a measure of communication between two brain regions) with the piriform cortex.

And the degree of this reduction was related to the increase in 2-OG and how much subjects changed their food choices when sleep deprived.

“When the piriform cortex does not properly communicate with the insula, then people start eating more energy-dense food,” Thorsten said.

The solution? Other than getting more sleep, it may help to pay closer attention to how our nose sways our food choices.

“Our findings suggest that sleep deprivation makes our brain more susceptible to enticing food smells, so maybe it might be worth taking a detour to avoid your local doughnut shop next time you catch a 6 a.m. flight,” Kahnt said.

Funding: The study was supported by the National Center for Advancing Translational Sciences, grant UL1652 TR001422, the National Blood Lung and Heart Institute grant T32 HL007909, the National Institute of Diabetes and Digestive and Kidney Diseases grant R21 DK118503 and the National Institute on Deafness and Other Communication Disorders grant R01655 DC015426, all of the National Institutes of Health.

Other Northwestern authors are first author Surabhi Bhutani, James D. Howard, Rachel Reynolds, Phyllis Zee and Jay A. Gottfried.

Sleep deprivation profoundly impacts food choices. When individuals are sleep-deprived, their dietary behavior shifts toward increased consumption of foods high in sugar and fat, leading to weight gain (Markwald et al., 2013Nedeltcheva et al., 2009). These effects on ingestive behavior are likely related to sleep-dependent changes in appetite-regulating compounds, including ghrelin (Rihm et al., 2019Spiegel et al., 2004b), leptin (Spiegel et al., 2004a), and endocannabinoids (Hanlon et al., 2016). Indeed, the endocannabinoid system (ECS) exerts strong effects on food intake (Bellocchio et al., 2010Di Marzo et al., 2001), and levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) and its structural analog 2-oleoylglycerol (2-OG) are enhanced in sleep-deprived individuals (Hanlon et al., 2016). While previous studies have tested the effects of sleep deprivation on the human brain (Greer et al., 2013Krause et al., 2017Muto et al., 2016Rihm et al., 2019), the neural pathways through which sleep-dependent alterations in the ECS influence food intake have not been investigated in humans.

One likely target for sleep-dependent neuromodulation of food intake is the olfactory system. Odors serve as powerful signals for the initiation and termination of feeding behavior (Saper et al., 2002Shepherd, 2006), and animal studies have shown that olfactory processing is modulated in a state-dependent manner (Julliard et al., 2007McIntyre et al., 2017Murakami et al., 2005). In rodents (Aimé et al., 2007Aimé et al., 2014) and humans (Hanci and Altun, 2016Stafford and Welbeck, 2011), olfaction is altered by hunger and satiety, and satiety reduces neural activity in olfactory brain regions in parallel with a suppression of feeding behavior (Boesveldt, 2017Gervais and Pager, 1979O’Doherty et al., 2000Prud’homme et al., 2009Soria-Gómez et al., 2014). Moreover, recent work across different species suggests a link between the ECS, olfactory processing, and food intake, such that endocannabinoids may directly modulate neural activity in olfactory circuits (Breunig et al., 2010Soria-Gómez et al., 2014). However, whether odor-evoked responses in the human olfactory system are similarly modulated by the ECS, and whether this accounts for the effects of sleep deprivation on food intake, is not known.

We hypothesized that sleep deprivation is associated with a cascade of metabolic and olfactory changes, ultimately steering food choices toward energy-dense options (Simon et al., 2015). We predicted that after a night of restricted sleep, relative levels of circulating ECS compounds will be increased (Hanlon et al., 2016), leading to changes in how olfactory brain regions in the medial temporal and basal frontal lobes respond to food odors (Soria-Gómez et al., 2014). We expected that such sleep-dependent changes in olfactory processing would manifest in odor-evoked activity patterns in piriform cortex (Howard and Gottfried, 2014Howard et al., 2009), and that effects on food intake would involve interactions with areas downstream of piriform cortex, such as the insula. Olfactory, gustatory, homeostatic, and visceral signals are integrated in the insula (Craig, 2002de Araujo et al., 2003Johnson et al., 2000Livneh et al., 2017Small et al., 2008), optimally positioning this region to regulate ingestive behavior in a state-dependent manner (Dagher, 2012de Araujo et al., 2006).

Northwestern University
Media Contacts:
Marla Paul – Northwestern University
Image Source:
The image is in the public domain.

Original Research: Open access
“Olfactory connectivity mediates sleep-dependent food choices in humans”. Surabhi Bhutani et al..
eLife doi:10.7554/eLife.49053.


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