Sleep deprivation, Olfactory Connectivity & Food Choices
Sleep deprivation has marked effects on food intake, shifting food choices toward energy-dense options
Here we test the hypothesis that neural processing in central olfactory circuits, in tandem with the endocannabinoid system (ECS), plays a key role in mediating this relationship.
We combined a partial sleep-deprivation protocol, pattern-based olfactory neuroimaging, and ad libitum food intake to testing how central olfactory mechanisms alter food intake after sleep deprivation. We found that sleep restriction increased levels of the ECS compound 2-oleoylglycerol (2-OG), enhanced the encoding of food odors in the piriform cortex, and shifted food choices toward energy-dense food items. Importantly, the relationship between changes in 2-OG and food choices was formally mediated by odor-evoked connectivity between the piriform cortex and insula, a region involved in integrating feeding-related signals. These findings describe a potential neurobiological pathway by which state-dependent changes in the ECS may modulate chemosensory processing to regulate food choices.
People who do not get enough sleep often start to favor sweet and fatty foods, which contributes to weight gain. While the exact mechanisms are still unknown, lack of sleep seems to change food preferences by influencing the levels of molecules that regulate food intake. In particular, it could have an effect on the endocannabinoid system, a complex network of molecules in the nervous system that controls biological processes such as appetite.
The sense of smell is also tightly linked to how and what organisms choose to eat. Recent experiments indicate that in rodents, endocannabinoids enhance food intake by influencing the activity of the brain areas that process odors. However, it is still unclear whether the brain regions that process odors play a similar role in humans.
To investigate, Bhutani et al. examined the impact of a four-hour night’s sleep on 25 healthy human volunteers. Blood analyses showed that after a short night, individuals had increased amounts of 2-oleoylglycerol, a molecule that is part of the endocannabinoid system. When sleep-deprived people were given the choice to eat whatever they wanted, those with greater levels of 2-oleoylglycerol preferred food higher in energy. Bhutani et al. also imaged the volunteers’ brains to examine whether these changes were connected to modifications in the way the brain processed smells. This revealed that, in people who did not sleep enough, an odor-processing region called the piriform cortex was encoding smells more strongly.
The piriform cortex is connected to another region, the insula, which integrates information about the state of the body to control food intake. Lack of sleep altered this connection, and this was associated with a preference for high-energy food. In addition, further analysis showed that changes in the amounts of 2-oleoylglycerol were linked to modifications in the connection between the two brain areas. Taken together, these results suggest that sleep deprivation influences the endocannabinoid system, which in turn alters the connection between the piriform and insular cortex, leading to a shift toward foods that are high in calories.
In the United States alone, one in three people sleeps less than six hours a night. Learning more about how sleep deprivation affects brain pathways and food choices may help scientists to develop new drugs or behavioral therapies for conditions like obesity.
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., 2013; Nedeltcheva et al., 2009). These effects on ingestive behavior are likely related to sleep-dependent changes in appetite-regulating compounds, including ghrelin (Rihm et al., 2019; Spiegel 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., 2010; Di 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., 2013; Krause et al., 2017; Muto et al., 2016; Rihm 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., 2002; Shepherd, 2006), and animal studies have shown that olfactory processing is modulated in a state-dependent manner (Julliard et al., 2007; McIntyre et al., 2017; Murakami et al., 2005). In rodents (Aimé et al., 2007; Aimé et al., 2014) and humans (Hanci and Altun, 2016; Stafford and Welbeck, 2011), olfaction is altered by hunger and satiety, and satiety reduces neural activity in olfactory brain regions in parallel with suppression of feeding behavior (Boesveldt, 2017; Gervais and Pager, 1979; O'Doherty et al., 2000; Prud'homme et al., 2009; Soria-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., 2010; Soria-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 the piriform cortex (Howard and Gottfried, 2014; Howard et al., 2009), and that effects on food intake would involve interactions with areas downstream of the piriform cortex, such as the insula. Olfactory, gustatory, homeostatic, and visceral signals are integrated in the insula (Craig, 2002; de Araujo et al., 2003; Johnson et al., 2000; Livneh et al., 2017; Small et al., 2008), optimally positioning this region to regulate ingestive behavior in a state-dependent manner (Dagher, 2012; de Araujo et al., 2006).
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