Gut-cholinergic Motoneuron Communication Regulates Lipid Metabolism in Caenorhabditis Elegans
Journal: Advanced Journal of Nursing DOI: 10.32629/ajn.v4i1.1212
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
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