Hepatic Vagal Afferents Convey Clock-Dependent Signals to Regulate Circadian Food Intake Patterns
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PROVIDER: PRJNA1044072 | ENA |
REPOSITORIES: ENA
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Project description:Circadian desynchrony induced by shiftwork or jetlag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chrono-disruption.
2024-12-18 | GSE248462 | GEO
Project description:Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.
2019-11-14 | GSE138651 | GEO
Project description:The vagus nerve has long been associated with the regulation of energy balance. However, the identity of the molecules mediating these effects remain largely unknown. Here, we used RNA sequencing to interrogate the molecular repertoire of the mouse vagal afferents. We found that Fgf3 mRNA is upregulated in the jugular-nodose ganglia under acute insulin resistance. Together, we provide evidence for efferent-like roles of the vagal afferents and identify Fgf3 as a novel vagal sensory-derived metabolic hormone that regulates insulin secretion and energy expenditure.
2024-08-04 | GSE239596 | GEO
Project description:An airway protection program revealed by sweeping genetic control of vagal afferents
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Project description:Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the principal chemosensors in the GI tract, but investigation of their role in behavior has been limited by the difficulty of selectively targeting these cells in vivo. Here we describe an intersectional genetic approach for manipulating EEC subtypes in behaving mice. We show that multiple EEC subtypes inhibit food intake but have different effects on learning. Conditioned flavor preference is driven by release of cholecystokinin whereas conditioned taste aversion is mediated by serotonin and substance P. These positive and negative valence signals are transmitted by vagal and spinal afferents, respectively. These findings establish a cellular basis for how chemosensing in the gut drives learning about food.
2022-05-24 | GSE203200 | GEO
Project description:Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. In order to elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488 conjugated Cholera toxin B allowed identification of neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser capture microdissection. Gene expression profiles of visceral afferent neurons, obtained by microarray hybridization, were analysed using multivariate spectral map analysis, SAM algorithm (Significance Analysis of Microarray data) and fold-difference filtering. A total of 1996 genes were found to be differentially expressed in DRG versus NG, including 41 G-protein coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, a detailed catalogue of all adrenergic and cholinergic, GABA, glutamate, serotonin and dopamine receptors, voltage-gated potassium, sodium and calcium channels and transient receptor potential cation channels present in visceral afferents is provided. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG visceral sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacologic agents modulating visceral sensation. Experiment Overall Design: Three separate experiments were performed. First, 5 whole dorsal root ganglia were compared to 7 whole nodose ganglia. Second, Laser captured visceral neurons derived from 5 dorsal root ganglia and 5 nodose ganglia were compared on MG-U74Av2. Third, Laser captured visceral neurons derived from 9 dorsal root ganglia and 11 nodose ganglia were compared on Mouse430_2.
2007-08-31 | E-GEOD-2917 | biostudies-arrayexpress
Project description:Virtually every mammalian tissue exhibits rhythmic expression in thousands of genes, which activate tissue-specific processes at appropriate times of the day. Much of this rhythmic expression is thought to be driven cell-autonomously by molecular circadian clocks present throughout the body. However, increasing evidence suggests that systemic signals, and more specifically rhythmic food intake (RFI), can regulate rhythmic gene expression independently of the circadian clock. To determine the relative contribution of cell autonomous clocks versus RFI in the regulation of rhythmic gene expression, we developed a system that allows long-term manipulation of the daily rhythm of food intake in the mouse, and analyzed liver gene expression by RNA-Seq in mice fed ad libitum, only at night, or arrhythmically (mouse eating 1/8th of their daily food intake every 3 hours). We show that 70% of the cycling mouse liver transcriptome loses rhythmicity under arrhythmic feeding. Remarkably, this loss of rhythmic gene expression under arrhythmic feeding is independent of the liver circadian clock, which continues to exhibit normal oscillations in core clock gene expression. Many genes that lose rhythmicity participate in the regulation of metabolic processes such as lipogenesis and glycogenesis, likely contributing to an increased sensitivity to insulin that was observed in arrhythmically-fed mice. We also show that night-restricted feeding significantly increases the number of rhythmically expressed genes as well as the amplitude of the rhythms. Together, these results indicate that metabolic transcription factors control a large fraction of the rhythmic mouse liver transcriptome, and demonstrate that systemic signals driven by rhythmic food intake play a more important role than the cell-autonomous circadian clock in driving rhythms in liver gene expression and metabolic functions.
2019-04-25 | GSE118967 | GEO
Project description:Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and on a moment-by-moment basis, enact vital reflexes to maintain respiratory function. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax, or airway compression. Here, we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses, and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, while ablating NEBs or vagal PVALB neurons eliminated gasping to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of PIEZO2 in NEBs also eliminated responses to airway closure. NEBs are dispensable for the Hering-Breuer inspiratory reflex, indicating that discrete terminal structures detect airway closure and inflation. Like Merkel cells involved in touch sensation, NEBs are PIEZO2-expressing epithelial cells, and moreover, are critical for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways, and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.
2024-03-06 | GSE252735 | GEO
Project description:Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. In order to elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488 conjugated Cholera toxin B allowed identification of neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser capture microdissection. Gene expression profiles of visceral afferent neurons, obtained by microarray hybridization, were analysed using multivariate spectral map analysis, SAM algorithm (Significance Analysis of Microarray data) and fold-difference filtering. A total of 1996 genes were found to be differentially expressed in DRG versus NG, including 41 G-protein coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, a detailed catalogue of all adrenergic and cholinergic, GABA, glutamate, serotonin and dopamine receptors, voltage-gated potassium, sodium and calcium channels and transient receptor potential cation channels present in visceral afferents is provided. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG visceral sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacologic agents modulating visceral sensation. Keywords: Cell type comparison
2005-12-21 | GSE2917 | GEO
Project description:Cytokines employ downstream Janus kinases (JAKs) to promote many chronic inflammatory disorders. JAK1-dependent type 2 cytokines drive allergic inflammation and patients with JAK1 gain-of-function (GOF) variants develop atopic dermatitis (AD) and asthma. To explore the tissue-specific role of JAK1, we inserted a human JAK1 GOF variant into mice and observed the spontaneous development of AD-like skin inflammation but unexpected resistance to allergic lung inflammation when JAK1 GOF expression was restricted to the stroma. Further, we identified the chemical denervation of both vagal and spinal visceral afferents exacerbated allergic lung inflammation, though selective denervation of spinal visceral afferent did not change the disease severity compared to control groups. Collectively, we suggested that neuron-intrinsic JAK1 in the vagal afferents protect against allergic lung inflammation.
2023-11-14 | GSE220497 | GEO