Gut-cholinergic Motoneuron Communication Regulates Lipid Metabolism in Caenorhabditis Elegans

Journal: Advanced Journal of Nursing DOI: 10.32629/ajn.v4i1.1212

Rui Dan

Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, Hubei, China

Abstract

Recent studies reveal the gut-brain axis, with its bidirectional signaling function, plays a crucial role in host physiological regulation. Through the gut-to-brain signaling, the nervous system can influence lipid metabolism and gut physiological function via brain-to-gut signaling. However, the mechanism of how the bidirectional signaling pathway of the gut-brain axis affects the host remains elusive. In this study, the author found that the lipid metabolism pathway of Caenorhabditis elegans (C. elegans) is regulated by the bidirectional communication of cholinergic motoneurons. The ASIC-1 protein, a homolog of mammalian acid-sensitive ion channel ASICs, impacts C. elegans lipid metabolism through expression in cholinergic motoneurons. Calcium imaging experiments revealed that C. elegans cholinergic motoneurons possess H+ sensitivity, which is dependent on their ASIC-1 expression. It has been reported that various Na+-H+ exchangers (NHXs) expressed by C. elegans intestinal epithelial cells can release H+ to act on ASIC-1 in cholinergic motoneurons. NHX-6, expressed by C. elegans intestinal epithelium, may regulate C. elegans lipid levels by releasing H+ to activate ASIC-1 expressed by cholinergic motoneurons. By using RNAi technology to knock down the genes that regulate cholinergic neurotransmitter signals in cholinergic motoneurons, the author found that the NHX-6-ASIC-1 signaling regulates body fat levels through cholinergic signaling. In vivo fluorescence imaging of C. elegans confirmed that the NHX-6-ASIC-1 signaling pathway reduces the expression level of the key lipid catabolic gene atgl-1 and increases the expression levels of the key synthetic metabolic genes dgat-2, fat-5, and fat-7. In summary, the results of the above studies indicate that the intestinal epithelial cell Na+-H+ exchanger NHX-6 releases H+, activating the acid-sensitive ion channel ASIC-1, which in turn regulates the activity of cholinergic motoneurons and the release of the neurotransmitter acetylcholine. This initiates a conserved intestinal signaling pathway that promotes lipid synthesis metabolism, ultimately affecting the body fat levels of the C. elegans.

Keywords

C. elegans, gut-cholinergic motoneuron communication, lipid metabolism, acid-sensitive ion channel, Na+-H+ exchanger

References

References
[1] Mattson M P, Duan W Z, Maswood N. How does the brain control lifespan? [J]. Ageing Res Rev, 2002, 1(2): 155-65.
[2] Rera M, Azizi M J, Walker D W. Organ-specific mediation of lifespan extension: More than a gut feeling? [J]. Ageing Res Rev, 2013, 12(1): 436-44.
[3] Wang Y B, de Lartigue G, Page A J. Dissecting the Role of Subtypes of Gastrointestinal Vagal Afferents [J]. Front Physiol, 2020, 11: 643.
[4] Wang Y, Leung V H, Zhang Y, et al. The role of somatosensory innervation of adipose tissues [J]. Nature, 2022, 609(7927): 569-74.
[5] Pavlov V A, Chavan S S, Tracey K J. Molecular and Functional Neuroscience in Immunity [J]. Annual review of immunology, 2018, 36: 783-812.
[6] Soto E, Ortega-Ramírez A, Vega R. Protons as Messengers of Intercellular Communication in the Nervous System [J]. 2018, 12(342).
[7] Williams E K, Chang R B, Strochlic D E, et al. Sensory Neurons that Detect Stretch and Nutrients in the Digestive System [J]. Cell, 2016, 166(1): 209-21.
[8] Akiba Y, Nakamura M, Nagata H, et al. Acid-sensing pathways in rat gastrointestinal mucosa [J]. J Gastroenterol, 2002, 37 Suppl 14: 133-8.
[9] Holzer P. Acid-sensing ion channels in gastrointestinal function [J]. Neuropharmacology, 2015, 94: 72-9.
[10] Rhoades J L, Nelson J C, Nwabudike I, et al. ASIC-1s Mediate Food Responses in an Enteric Serotonergic Neuron that Controls Foraging Behaviors [J]. Cell, 2019, 176(1-2): 85-97 e14.
[11] Luoping, Sun Biying, Li Qian, et al. Characteristics of acid-sensitive currents in primary afferent neurons of the mouse small intestine vagus nerve [J]. Journal of Shanghai Jiao Tong University: Medical Edition, 2010, (7): 783-7.
[12] Irazoqui J E, Urbach J M, Ausubel F M. Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates [J]. Nat Rev Immunol, 2010, 10(1): 47-58.
[13] Cook S J, Jarrell T A, Brittin C A, et al. Whole-animal connectomes of both Caenorhabditis elegans sexes [J]. Nature, 2019, 571(7763): 63-71.
[14] Wani K A, Goswamy D, Irazoqui J E. Nervous system control of intestinal host defense in C. elegans [J]. Curr Opin Neurobiol, 2020, 62: 1-9.
[15] Srinivasan S. Regulation of body fat in Caenorhabditis elegans [J]. Annu Rev Physiol, 2015, 77: 161-78.
[16] Lemieux G A, Ashrafi K. Neural Regulatory Pathways of Feeding and Fat in Caenorhabditis elegans [J]. Annu Rev Genet, 2015, 49: 413-38.
[17] Flavell S W, Gordus A. Dynamic functional connectivity in the static connectome of Caenorhabditis elegans [J]. Curr Opin Neurobiol, 2022, 73: 102515.
[18] Matty M A, Lau H E, Haley J A, et al. Intestine-to-neuronal signaling alters risk-taking behaviors in food-deprived Caenorhabditis elegans [J]. PLoS Genet, 2022, 18(5): e1010178.
[19] Shi Y, Qin L, Wu M, et al. Gut neuroendocrine signaling regulates synaptic assembly in C. elegans [J]. EMBO Rep, 2022: e53267.
[20] Urrutia A, García-Angulo V A, Fuentes A, et al. Bacterially produced metabolites protect C. elegans neurons from degeneration [J]. PLoS Biol, 2020, 18(3): e3000638.
[21] Li Z, Liu J, Zheng M, et al. Encoding of both analog- and digital-like behavioral outputs by one C. elegans interneuron [J]. Cell, 2014, 159(4): 751-65.
[22] Wen Q, Po M D, Hulme E, et al. Proprioceptive Coupling within motoneurons Drives C. elegans Forward Locomotion [J]. Neuron, 2012, 76(4): 750-61.
[23] Pfeiffer J, Johnson D, Nehrke K. Oscillatory transepithelial H(+) flux regulates a rhythmic behavior in C. elegans [J]. Curr Biol, 2008, 18(4): 297-302.
[24] Beg A A, Ernstrom G G, Nix P, et al. Protons act as a transmitter for muscle contraction in C-elegans [J]. Cell, 2008, 132(1): 149-60.
[25] Voglis G, Tavernarakis N. A synaptic DEG/ENaC ion channel mediates learning in C. elegans by facilitating dopamine signalling [J]. EMBO J, 2008, 27(24): 3288-99.
[26] Kaulich E, Grundy L J, Schafer W R, et al. The diverse functions of the DEG/ENaC family: linking genetic and physiological insights [J]. J Physiol, 2022.
[27] Srinivasan S, Sadegh L, Elle I C, et al. Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms [J]. Cell metabolism, 2008, 7(6): 533-44.
[28] Wang S J, Wang Z W. Track-a-worm, an open-source system for quantitative assessment of C. elegans locomotory and bending behavior [J]. PLoS One, 2013, 8(7): e69653.
[29] Du J, Reznikov L R, Price M P, et al. Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala [J]. Proc Natl Acad Sci U S A, 2014, 111(24): 8961-6.
[30] Wemmie J A, Taugher R J, Kreple C J. Acid-sensing ion channels in pain and disease [J]. Nat Rev Neurosci, 2013, 14(7): 461-71.
[31] Nehrke K, Melvin J E. The NHX family of Na+-H+ exchangers in Caenorhabditis elegans [J]. The Journal of biological chemistry, 2002, 277(32): 29036-44.
[32] Rand J B. Acetylcholine [J]. WormBook, 2007: 1-21.
[33] Pereira L, Kratsios P, Serrano-Saiz E, et al. A cellular and regulatory map of the cholinergic nervous system of C. elegans [J]. Elife, 2015, 4.
[34] Yang R, Li Y, Wang Y, et al. NHR-80 senses the mitochondrial UPR to rewire citrate metabolism for lipid accumulation in Caenorhabditis elegans [J]. Cell reports, 2022, 38(2): 110206.
[35] Li Y, Ding W, Li C Y, et al. HLH-11 modulates lipid metabolism in response to nutrient availability [J]. Nature communications, 2020, 11(1): 5959.
[36] Brock T J, Browse J, Watts J L. Genetic Regulation of Unsaturated Fatty Acid Composition in C. elegans [J]. PLoS genetics, 2006, 2(7): e108.

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