PhD Scientific Days 2021

MO_III_L: Molecular Sciences III. Lectures

SIR-2.1 regulates lipolysis via HSF-1 in C. elegans

Text of the abstract

Introduction
Obesity is a risk factor for the leading causes of death in our modern societies. Many of the hallmarks of obesity and metabolic syndrome have large overlaps with hallmarks of another important risk factor for various diseases: ageing. The metabolic regulator SIR-2.1 protein deacetylase and the proteostasis regulator heat shock transcription factor HSF-1 are both involved in the regulation of lifespan, ageing and the longevity-promoting effects of diatery restriction.

Aims
The aim of this study is to investigate how these important regulators might modulate metabolism through lipid mobilization.

Method
We took use of various C. elegans techniques, such as lipid staining by the dye Oil Red O to monitor the lipid content of animals, quantitative PCR measurements to register changes in lipase expressions, fluorescently labelled nematodes for the same reason and various mutant strains to get a closer look into the underlying mechanisms.

Results
We were able to confirm SIR-2.1’s necessity for lipid mobilization and the induction of lipase expression, but also found that it acts through blocking HSF-1’s inhibitory effect on this metabolic process. We also found this interaction to be tissue specific, since both proteins are required for their effects in the intestine – the place for lipid storage. Furthermore, our results indicate that HSF-1 might exert its influence by utilizing the microRNA gene regulatory system.

Conclusion
Taken together these data point in the direction of an intricate regulatory mechanism linking energy-metabolism to proteostasis and potentially, lifespan.

Funding
This work was funded by ÚNKP-20-4-II-SE-6

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine