Science and Technology Production
Congress
Authorship
Scattolini, A
;
Lopez Crespo, R
;
Ruffini, S
;
Baldaseroni, L
;
de Mendoza, D
;
MANSILLA, MARIA CECILIA
Date
2026
Publishing House and Editing Place
EMBO
Summary
Information provided by the agent in
SIGEVA
In mammals, changes in hypothalamic malonyl-CoA concentration have been postulated to contribute to regulation of appetite control, probably through an allosteric interaction with a brain-specific carnitine palmitoyltransferase-1 (CPT1). In a previous work we increased malonyl-CoA concentration treating C. elegans with the mycotoxin cerulenin, an inhibitor of Fatty Acid Synthase (FAS), or by performing knock-down experiments to block FAS I expression in a RNAi neuronal-sensitive strain (TU3401)...
In mammals, changes in hypothalamic malonyl-CoA concentration have been postulated to contribute to regulation of appetite control, probably through an allosteric interaction with a brain-specific carnitine palmitoyltransferase-1 (CPT1). In a previous work we increased malonyl-CoA concentration treating C. elegans with the mycotoxin cerulenin, an inhibitor of Fatty Acid Synthase (FAS), or by performing knock-down experiments to block FAS I expression in a RNAi neuronal-sensitive strain (TU3401). In both cases, we observed a similar decrease in pump rates, indicating that this nematode could be a valuable model to contribute to the understanding of homologous processes in mammals.The fasn-1 RNAi assay was now performed using the wild-type N2 strain, which is resistant to RNAi in neuronal tissues, and MAH677 strain, which expresses the transporter SID-1 exclusively in neurons. We only observed significant differences in food intake in MAH677. Concomitant cerulenine treatment and knockdown of pod-2, which encodes acetyl-CoA carboxylase (the enzyme that synthesizes malonyl-CoA), restored basal pumping rates, but only in MAH677, indicating that changes in neuronal malonyl-CoA concentration modulates pharyngeal activity. Through computational analysis of the C. elegans genome, we identified eight orthologues of the human CPTs proteins. By decreasing the expression of CPT-1 and CPT-5 in neurons we determined that these proteins are involved in the malonyl-CoA-mediated appetite-satiety signaling cascade, while silencing CPT-4 did not produce changes in feeding behavior. The purification of CPT1 and CPT5 for the determination of their interactomes is currently under development.Our findings reveal a conserved role for neuronal malonyl-CoA as a central metabolic signal in appetite regulation. By establishing C. elegans as a model for manipulating malonyl-CoA specifically in each tissue, we open the door to future mechanistic studies of how cellular metabolic state translates into behavioral responses.
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Key Words
APETITE REGULATIONMALONIL-COACAENORHABDITIS ELEGANS