
The sirtuin SIR-2.1 activates lipolysis during starvation by suspending the HSF-1-mediated repression of the adipose triglyceride lipase ATGL-1 in the C. elegans intestine.


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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.

### Competing Interest Statement

The authors have declared no competing interest.

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

an-intestinal-pathway-involving-the-sirtuin-sir-2-1-heat-shock-factor-hsf-1-and-adipose-triglyceride-lipase-atgl-1-regulates-lipolysis-in-c-elegans


An Intestinal Pathway Involving the Sirtuin SIR-2.1, Heat Shock Factor HSF-1, and Adipose Triglyceride Lipase ATGL-1 Regulates Lipolysis in C. elegans
