Mood and Food, Cravings, and Addiction
Emily Crews Splane, Neil E. Rowland, Anaya Mitra in Psychology of Eating, 2019
An increasing amount of evidence indicates a role of the orexin (also referred to as hypocretin) system in drug abuse and palatable food consumption (Aston-Jones, 2010). Orexin receptors have been found in the hypothalamus (associated with maintaining homeostasis and motivation) and mesolimbic regions (associated with reward). Orexin signaling seems to modulate dopamine activity within the mesolimbic region, enhancing the reward of pleasurable stimuli and increasing the motivation to seek out such stimulation. However, orexin antagonists do not block food-deprived rats’ consumption of chow, indicating that orexin activity is involved in hedonic food consumption and drug use, but not hunger-induced food consumption (Choi et al., 2010).
Obesity and Obstructive Sleep Apnoea
Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei in Manual of Hypertension of the European Society of Hypertension, 2019
Amongst numerous neurohormones, the hypocretin system (orexin-A) has been found to play an important role in the regulation of sleep and arousal states, feeding and energy balance, centrally mediated CV regulatory actions and other peripheral functions (58). The vast majority of studies documenting orexin deficiency come from patients demonstrating narcolepsy or primary hypersomnia (59). Given the presence of sleep disturbances (i.e. daytime sleepiness, wakefulness) in OSA patients, it has been suggested that orexin may be implicated in the pathogenesis of disease. Previous studies documented low levels of orexin-A in OSA patients (60–62), which decrease in parallel with the severity of disease (60). Abnormally low orexin-A levels have been found in untreated patients with severe OSA (mean AHI 54 ± 4 events per hour) when compared to healthy controls (61). Treatment of the OSA cohort with CPAP for at least 1 year also resulted in lower values of orexin-A compared to healthy controls (61). A reduced orexin-A level appeared to be independent of the number of apnoeas during sleep, the presence of daytime sleepiness or obesity (61).
Neurobiology of Mood Disorders
Dr. Ather Muneer in Mood Disorders, 2018
Circadian rhythms in the liver, stomach, adipose tissue and gut are robust, leading to distinct 24-hour cycles in metabolic functions. Peptides involved in metabolism and feeding like ghrelin, orexin, leptin and cholecystokinin (CCK) exhibit a marked circadian rhythm in expression. In human blood samples, leptin is increased during the night, orexin levels are elevated during the day and ghrelin and CCK are high prior to meals and at night.30 Both leptin and ghrelin signal through orexin neurons in the brain, enhancing wakefulness when stimulated by ghrelin and promoting sleep when inhibited by leptin. In narcolepsy, a condition in which individuals experience sudden sleep bouts, there is dysfunction of the orexin system, linking regulation of feeding and sleep to a small population of hypothalamic neurons. CCK is more widely expressed throughout the brain and gut including high levels of expression in GABAergic interneurons of the prefrontal cortex, dopaminergic neurons of the VTA, and the shell of the SCN.31 These peptides and others involved in feeding behaviors are out of sync in the ClockΔ19 mice, demonstrating that their expression is regulated by the core molecular clock. Furthermore, ClockΔ19 mice gain weight rapidly on a high fat diet and display many features of obesity and the metabolic syndrome.32
Sucrose drinking mimics effects of nucleus accumbens µ-opioid receptor stimulation on fat intake and brain c-Fos-expression
Published in Nutritional Neuroscience, 2022
L.L. Koekkoek, A. Masís-Vargas, T. Kool, L. Eggels, L.L. van der Gun, K. Lamuadni, M. Slomp, C. Diepenbroek, A. Kalsbeek, S.E. la Fleur
We found that overall, DAMGO increased the percentage of c-Fos+orexin-positive cells and that this increase was mainly driven by the group that was drinking sucrose. In the water-drinking groups, the difference between vehicle and DAMGO treated animals was much smaller than previously reported [11,31]. This discrepancy might be explained by differences in the timing of the experiment [32] (end of the light period versus the beginning of the light period) or the motivational state (rats in our experiments had continuous access to the fcHF diet, compared to two hours a day [11,31]), which both have been shown to affect orexin neuronal activity [32–34]. Furthermore, the observed c-Fos+orexin-positive cell pattern does not reflect the changes we found in fat intake. Orexin neurons project to a variety of brain areas [35], but only orexin signaling in the ventral tegmental area, and not the arcuate nucleus or paraventricular hypothalamus, has been shown to be crucial for the effects of intra-NAC DAMGO on fat intake [11]. This indicates that orexin signaling is not always linked to increased fat intake, depending on where the orexin is released. Therefore, we speculate that the orexin neurons that are activated in the fcHF W vehicle or fcHF S DAMGO group (in which we did not observe an increase in fat intake) might be primarily orexin neurons that project to other brain areas than the ventral tegmental area.
Nutritional efficacy of Astaxanthin in modulating orexin peptides and fatty acid level during adult life of rats exposed to perinatal undernutrition stress
Published in Nutritional Neuroscience, 2022
Megha Bhat Agni, Pramukh Subrahmanya Hegde, Harshini Ullal, K.M. Damodara Gowda
The present study also demonstrated the increase in Orexin-A and B peptides at different time points in the postnatal life of rats exposed to nutrition stress during gestation and lactation period and its modulation upon administration of Astaxanthin. The orexin systems (hypocretins) are vital for responding to stress and modulating behaviors associated with cognition, sleep-wake states, and appetite [29]. As reported earlier, a central orexin system increases food intake. In contrast, antagonists of orexin receptors decrease food intake, as noted earlier in transgenic mice. The gradual loss of orexin neurons showed feeding abnormalities, leading to obesity despite the reduced food intake [30]. Previous studies reported that orexin neurons in the dorsomedial hypothalamic areas and perifornical areas are associated with stress and arousal, while those in the lateral hypothalamus on addiction [31, 32].
Brain site-specific regulation of hedonic intake by orexin and DYN peptides: role of the PVN and obesity
Published in Nutritional Neuroscience, 2022
P. Mattar, S. Uribe-Cerda, C. Pezoa, T. Guarnieri, C. M. Kotz, J. A. Teske, E. Morselli, C. Perez-Leighton
We used the CAF diet, which closely resembles human obesogenic diets [39], to examine whether expression of KOR and orexin receptors across different brain sites correlated with food preference or caloric intake in obese mice. Mice fed CAF diet showed increased expression OX1R and OX2R in the DH (a sample enriched in PVN). Administration of orexin peptides in PVN do not increase hedonic intake in lean mice, suggesting that this obesity-induced change in orexin receptor expression might reflect a compensatory mechanism against excessive palatable food intake, as reported in mice fed a high-fat [40]. Also, as the DH samples contained the PVN, this upregulation of orexin receptors could underlie a mechanism to regulate energy balance by increased energy expenditure through physical activity [36]. Overall, these data suggest that obesity may alter orexin function in PVN, and future experiments should determine whether these effects are related to increased energy expenditure.
Related Knowledge Centers
- Appetite
- Cataplexy
- Lateral Hypothalamus
- Neuropeptide
- Peptide
- Wakefulness
- Narcolepsy
- Arousal
- Orexin-A
- Neuron