Soti, C. | Search bioRxiv

bioRxiv2024

An intestinal Sir2-HSF1-ATGL1 pathway regulates lipolysis in C. elegans

Proteostasis maintenance and lipid metabolism are critical for survival and promote longevity, however, their coordination is largely unclear. Here we show that the heat shock factor HSF-1 and the proteostasis state regulates lipolysis in C. elegans. We find that in response to starvation, the sirtuin 1 ortholog SIR-2.1 activates lipolysis by upregulation of the adipose triglyceride lipase ATGL-1. In feeding worms, intestinal HSF-1 represses ATGL-1 expression and lipolysis via the microRNA system. In starving worms, SIR-2.1 suspends a miR-53- mediated suppression of lipolysis by inhibiting its HSF-1-dependent expression. The apparent antagonism of SIR-2.1 and HSF-1, distinct from their synergism at heat shock promoters suggests a context-specific regulation of HSF-1 by SIR-2.1. We demonstrate that the SIR-2.1 and protein kinase A pathways are both indispensable, and independently converge on ATGL- 1 for lipolysis. HSF-1 activation by proteostasis disturbances inhibits starvation-induced lipid mobilization, whereas its age-related decline limits fat deposition through atgl-1. Our findings reveal a crosstalk between proteostasis and lipid/energy metabolism, which may modulate stress resilience and aging.

molecular biology↗

bioRxiv2020

Toxic stress-specific cytoprotective responses regulate learned behavioral decisions in C. elegans

BackgroundProtection of organismal integrity involve physiological stress responses and behavioral defenses. Recent studies in the roundworm Caenorhabditis elegans have shown that pathogen and toxin exposure simultaneously stimulate cellular stress and detoxification responses and aversive behavior. However, whether a coordinate regulation exists between cellular and neurobehavioral defenses remains unclear. ResultsHere we show that exposure of C. elegans to high concentrations of naturally attractive food-derived odors, benzaldehyde and diacetyl, induces toxicity and aversive behavior. Benzaldehyde preconditioning activates systemic cytoprotective stress responses involving DAF-16/FOXO, SKN-1/Nrf and Hsp90 in somatic cells, which confer behavioral tolerance to benzaldehyde and cross-tolerance to the structurally similar methyl-salicylate, but not to the structurally unrelated diacetyl. In contrast, diacetyl preconditioning augments diacetyl avoidance and does not induce apparent molecular defenses. Reinforcement of the experiences using massed training forms relevant associative memories. Memory retrieval by the odor olfactory cues leads to avoidance of food contaminated by diacetyl and context-dependent behavioral decision to avoid benzaldehyde only if there is an alternative, food-indicative odor. ConclusionsOur findings reveal a regulatory link between physiological stress responses and learned behavior which facilitates self-protection in real and anticipated stresses. The potential conservation of this somato-neuronal connection might have relevance in maladaptive avoidant human behaviors.

neuroscience↗