I would like to warmly invite you to our next Nencki Institute Seminar on the 18th of January at 3pm in the CN lecture hall. We will host dr. Toufic Kassouf. Dr. Kassouf's lecture will be entitled: "Impact of ubiquitin-dependent signaling events on regulation of adipose tissue function".

Abstract

The ubiquitin pathway is implicated in almost every cellular pathway described. However, little is known about the importance of ubiquitin in the regulation of metabolism in adipose tissue. Adipocytes acquire a unique morphology, consisting of a lipid droplet occupying the majority of the intracellular region. The major function of brown adipocytes is to dissipate energy in the form of heat. The main function of white adipocytes is to store energy as triglycerides (TGs) when energy is available in excess. Upon food deprivation, TGs stored in lipid droplets are degraded in the process of lipolysis. Adrenaline acting via β-adrenergic receptors is the major factor promoting catabolism of TGs.

To investigate the global changes in ubiquitination of proteome of brown and white adipocytes, two new adipocytic cell lines brown and white, T37i and 3T3L1 inducible expressing 6His-ubiquitin respectively were generated. After differentiation of both cell lines, ubiquitinated proteins were enriched by immunoprecipitation and analyzed by mass spectrometry (MS). Interestingly, our results indicate that among other ubiquitinated proteins identically expressed in both cell lines, an E3 ubiquitin-ligase zinc finger protein 598 (ZNF598) is markedly higher ubiquitinated in brown than white adipocytes. ZNF598 is known to play a key role in the translation surveillance pathways and ribosome quality control (RQC). Our results suggest that the levels of ZNF598 correlate with mitochondrial fitness in brown adipocytes.

In parallel, a Ubiscan analysis for profiling endogenous levels of ubiquitin on the lysate of differentiated adipocytes derived from primary stromal vascular cells from adipose tissue of mice upon adrenergic stimulation was established. Among the others, we discovered that the E3 ligase Tripartite Motif family 32 (TRIM32), is activated upon β-adrenergic stimulation of adipocytes. Our results show that TRIM32 suppresses the activity of AMPK and reduces the lipolysis rate in adipocytes.

Focusing mainly on the signaling pathways of ZNF598 and TRIM32 aims to answer how these specific players will present a major impact on processes such as thermogenesis and lipolysis.

The lecture will be followed by a get together.

With best wishes
Tomasz Wypych