scholarly journals Neuronal SKN-1B Modulates Nutritional Signalling Pathways and Mitochondrial Networks to Control Satiety

2020 ◽  
Author(s):  
Nikolaos Tataridas-Pallas ◽  
Maximillian Thompson ◽  
Alexander Howard ◽  
Ian Brown ◽  
Marina Ezcurra ◽  
...  

AbstractThe feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism and respiration, because can mediate the increased lifespan incurred by dietary restriction. We show that actually SKN-1B is not essential for dietary restriction longevity and instead, controls a variety of food-related behaviours. It acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-β), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins.

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009358
Author(s):  
Nikolaos Tataridas-Pallas ◽  
Maximillian A. Thompson ◽  
Alexander Howard ◽  
Ian Brown ◽  
Marina Ezcurra ◽  
...  

The feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism, respiration and the increased lifespan incurred by dietary restriction. Here we show that SKN-1B acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-β), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Hayao Ohno ◽  
Morikatsu Yoshida ◽  
Takahiro Sato ◽  
Johji Kato ◽  
Mikiya Miyazato ◽  
...  

Peptide signaling controls many processes involving coordinated actions of multiple organs, such as hormone-mediated appetite regulation. However, the extent to which the mode of action of peptide signaling is conserved in different animals is largely unknown, because many peptides and receptors remain orphan and many undiscovered peptides still exist. Here, we identify two novel Caenorhabditis elegans neuropeptides, LURY-1-1 and LURY-1-2, as endogenous ligands for the neuropeptide receptor-22 (NPR-22). Both peptides derive from the same precursor that is orthologous to invertebrate luqin/arginine-tyrosine-NH2 (RYamide) proneuropeptides. LURY-1 peptides are secreted from two classes of pharyngeal neurons and control food-related processes: feeding, lifespan, egg-laying, and locomotory behavior. We propose that LURY-1 peptides transmit food signals to NPR-22 expressed in feeding pacemaker neurons and a serotonergic neuron. Our results identified a critical role for luqin-like RYamides in feeding-related processes and suggested that peptide-mediated negative feedback is important for satiety regulation in C. elegans.


2017 ◽  
Author(s):  
Michael P. O’Donnell ◽  
Pin-Hao Chao ◽  
Jan E. Kammenga ◽  
Piali Sengupta

ABSTRACTAnimals integrate external cues with information about internal conditions such as metabolic state to execute the appropriate behavioral and developmental decisions. Information about food quality and quantity is assessed by the intestine and transmitted to modulate neuronal functions via mechanisms that are not fully understood. The conserved Target of Rapamycin complex 2 (TORC2) controls multiple processes in response to cellular stressors and growth factors. Here we show that TORC2 coordinates larval development and adult behaviors in response to environmental cues and feeding state in the bacterivorous nematode C. elegans. During development, pheromone, bacterial food, and temperature regulate expression of the daf-7 TGF-β and daf-28 insulin-like peptide in sensory neurons to promote a binary decision between reproductive growth and entry into the alternate dauer larval stage. We find that TORC2 acts in the intestine to regulate neuronal expression of both daf-7 and daf-28, which together reflect bacterial-diet dependent feeding status, thus providing a mechanism for integration of food signals with external cues in the regulation of neuroendocrine gene expression. In the adult, TORC2 similarly acts in the intestine to modulate food-regulated foraging behaviors via the PDFR-1 neuropeptide receptor. We also demonstrate that genetic variation affects food-dependent larval and adult phenotypes, and identify quantitative trait loci (QTL) associated with these traits.Together, these results suggest that TORC2 acts as a hub for communication of feeding state information from the gut to the brain, thereby contributing to modulation of neuronal function by internal state.AUTHOR SUMMARYDecision-making in all animals, including humans, involves weighing available information about the external environment as well as the animals’ internal conditions. Information about the environment is obtained via the sensory nervous system, whereas internal state can be assessed via cues such as levels of hormones or nutrients. How multiple external and internal inputs are processed in the nervous system to drive behavior or development is not fully understood. In this study, we examine how the nematode C. elegans integrates dietary information received by the gut with environmental signals to alter nervous system function. We have found that a signaling complex, called TORC2, acts in the gut to relay nutrition signals to alter hormonal signaling by the nervous system in C. elegans. Altered neuronal signaling in turn affects a food-dependent binary developmental decision in larvae, as well as food-dependent foraging behaviors in adults. Our results provide a mechanism by which animals prioritize specific signals such as feeding status to appropriately alter their development and/or behavior.


2021 ◽  
Author(s):  
Amy K Webster ◽  
Rojin Chitrakar ◽  
Maya Powell ◽  
Jingxian Chen ◽  
Kinsey Fisher ◽  
...  

Starvation resistance is a fundamental, disease-relevant trait, but the genetic basis of its natural variation is unknown. We developed a synthetic population-sequencing approach to measure starvation resistance for many wild C. elegans strains simultaneously. We identified three quantitative trait loci with variants in 16 insulin/EGF receptor-like domain (irld) family members. We show that four irld genes affect starvation resistance by regulating insulin/IGF signaling. We propose that IRLD proteins bind insulin-like peptides to modify signaling in the sensory nervous system thereby affecting organismal physiology. This work demonstrates efficacy of using population sequencing to dissect a complex trait, identifies irld genes that regulate insulin/IGF signaling, and shows that an expanded gene family modifies a deeply conserved signaling pathway to affect a fitness-proximal trait.


2011 ◽  
Vol 71 (10) ◽  
Author(s):  
J Arnold ◽  
ML Barcena de Arellano ◽  
C Rüster ◽  
A Schneider ◽  
S Mechsner

The control of movement is essential for animals traversing complex environments and operating across a range of speeds and gaits. We consider how animals process sensory information and initiate motor responses, primarily focusing on simple motor responses that involve local reflex pathways of feedback and control, rather than the more complex, longer-term responses that require the broader integration of higher centers within the nervous system. We explore how local circuits facilitate decentralized coordination of locomotor rhythm and examine the fundamentals of sensory receptors located in the muscles, tendons, joints, and at the animal’s body surface. These sensors monitor the animal’s physical environment and the action of its muscles. The sensory information is then carried back to the animal’s nervous system by afferent neurons, providing feedback that is integrated at the level of the spinal cord of vertebrates and sensory-motor ganglia of invertebrates.


Author(s):  
Joseph Ayers

This chapter describes how synthetic biology and organic electronics can integrate neurobiology and robotics to form a basis for biohybrid robots and synthetic neuroethology. Biomimetic robots capture the performance advantages of animal models by mimicking the behavioral control schemes evolved in nature, based on modularized devices that capture the biomechanics and control principles of the nervous system. However, current robots are blind to chemical senses, difficult to miniaturize, and require chemical batteries. These obstacles can be overcome by integration of living engineered cells. Synthetic biology seeks to build devices and systems from fungible gene parts (gene systems coding different proteins) integrated into a chassis (induced pluripotent eukaryotic cells, yeast, or bacteria) to produce devices with properties not found in nature. Biohybrid robots are examples of such systems (interacting sets of devices). A nascent literature describes genes that can mediate organ levels of organization. Such capabilities, applied to biohybrid systems, portend truly biological robots guided, controlled, and actuated solely by life processes.


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