Role of the transcription factor CREB3L1 in the regulation of lipids homeostasis

DI GIUSTO, P; FUNES CHABÁN, MACARENA; PAZ-MONTOYA JONATHAN; D?ANGELO GIOVANNI; ALVAREZ, CECILIA

Mendoza

Congreso; SAIB; 2022

SAIB

The transcription factor CREB3L1 regulates the expression of proteins involved in the secretory pathway (transport factors) as well as the expression of tissue-specific genes that require the secretory pathway to reach their final localization. We have previously shown that, in thyroid cells, CREB3L1 acts as a downstream effector of the Thyroid Stimulating Hormone (TSH) inducing the expression of proteins of the secretory pathway along with an expansion of the Golgi volume. We hypothesize that CREB3L1 also modulates the lipids homeostasis allowing thyroid cells to adapt to TSH stimulation. In this regards, lipidomic analysis of the rat thyroid follicular cell line PCCL3 shows that CREB3L1 knockdown (by siCREB3L1) induces higher expression levels of certain phosphatidylcholines (PC) and LysoPC species. Furthermore, both the CREB3L1 overexpression (by using CREB3L1CA) or TSH stimulation increase the same lipids species such as triacylglycerols (TAG) and lysobisphosphatidic acid (LBPA), as well as the metabolic processes associated with these lipids. In contrast, the lipids that increase in siCREB3L1 treated cells bear some degree of similarity to those that increase in TSH-deprived cells. This is comparable to what occurs in the absence of TSH (where CREB3L1 levels are low). These results highlight the role of CREB3L1 in the regulation of lipids homeostasis in thyroid cells