Methylglyoxal-derived hydroimidazolone, MG-H1, increases food intake by altering tyramine signaling via the GATA transcription factor ELT-3 in Caenorhabditis elegans .

Autor:	Muthaiyan Shanmugam M; The Buck Institute for Research on Aging, Novato, United States., Chaudhuri J; The Buck Institute for Research on Aging, Novato, United States., Sellegounder D; The Buck Institute for Research on Aging, Novato, United States., Sahu AK; The Buck Institute for Research on Aging, Novato, United States., Guha S; The Buck Institute for Research on Aging, Novato, United States., Chamoli M; The Buck Institute for Research on Aging, Novato, United States., Hodge B; The Buck Institute for Research on Aging, Novato, United States., Bose N; The Buck Institute for Research on Aging, Novato, United States., Amber C; Department of Chemistry, University of California, Berkeley, Berkeley, United States., Farrera DO; Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, United States., Lithgow G; The Buck Institute for Research on Aging, Novato, United States., Sarpong R; Department of Chemistry, University of California, Berkeley, Berkeley, United States., Galligan JJ; Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, United States., Kapahi P; The Buck Institute for Research on Aging, Novato, United States.; Department of Urology, University of California, San Francisco, San Francisco, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Sep 20; Vol. 12. Date of Electronic Publication: 2023 Sep 20.
DOI:	10.7554/eLife.82446
Abstrakt:	The Maillard reaction, a chemical reaction between amino acids and sugars, is exploited to produce flavorful food ubiquitously, from the baking industry to our everyday lives. However, the Maillard reaction also occurs in all cells, from prokaryotes to eukaryotes, forming advanced glycation end-products (AGEs). AGEs are a heterogeneous group of compounds resulting from the irreversible reaction between biomolecules and α-dicarbonyls (α-DCs), including methylglyoxal (MGO), an unavoidable byproduct of anaerobic glycolysis and lipid peroxidation. We previously demonstrated that Caenorhabditis elegans mutants lacking the glod-4 glyoxalase enzyme displayed enhanced accumulation of α-DCs, reduced lifespan, increased neuronal damage, and touch hypersensitivity. Here, we demonstrate that glod-4 mutation increased food intake and identify that MGO-derived hydroimidazolone, MG-H1, is a mediator of the observed increase in food intake. RNAseq analysis in glod-4 knockdown worms identified upregulation of several neurotransmitters and feeding genes. Suppressor screening of the overfeeding phenotype identified the tdc-1 -tyramine- tyra-2/ser-2 signaling as an essential pathway mediating AGE (MG-H1)-induced feeding in glod-4 mutants. We also identified the elt-3 GATA transcription factor as an essential upstream regulator for increased feeding upon accumulation of AGEs by partially controlling the expression of tdc-1 gene. Furthermore, the lack of either tdc-1 or tyra-2/ser-2 receptors suppresses the reduced lifespan and rescues neuronal damage observed in glod-4 mutants. Thus, in C. elegans , we identified an elt-3 regulated tyramine-dependent pathway mediating the toxic effects of MG-H1 AGE. Understanding this signaling pathway may help understand hedonistic overfeeding behavior observed due to modern AGE-rich diets. Competing Interests: MM, JC, DS, AS, SG, MC, BH, NB, CR, DF, GL, RS, JG No competing interests declared, PK Reviewing editor, eLife (© 2023, Muthaiyan Shanmugam et al.)
Databáze:	MEDLINE
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