Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Pena de la Sancha, P.
Regulation of sterol regulatory element binding protein (SREBP)-1c hepatic lipogenesis by adipose triglyceride lipase (ATGL)
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2025. pp. 76
[OPEN ACCESS]
FullText
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Höfler Gerald
- Kratky Dagmar
- Altmetrics:
- Abstract:
- Sterol Regulatory Element-Binding Proteins (SREBPs) are a group of transcription factors synthesized in the Endoplasmic Reticulum (ER) membrane that regulate cellular lipogenesis. Among the SREBP isoforms (SREBP-1a, -1c, and -2), SREBP-1c preferentially activates the transcription of genes required for the synthesis of fatty acids (FAs) and triglycerides (TGs). Conversely, during fasting, lipogenesis is suppressed, and the hydrolysis of TGs stored in the adipose tissue is activated, releasing glycerol and FAs that are transported to different tissues to provide energy in a process known as lipolysis. Adipose Triglyceride Lipase (ATGL) is the enzyme that catalyzes the first and limiting step in lipolysis within lipid droplets (LDs). In addition, ATGL has an affinity for the hydrolysis of unsaturated fatty acids (uFAs), which have been shown to regulate the proteolytic activation of SREBP-1c in vitro. Therefore, we propose that the FAs derived from ATGL lipolysis can influence SREBP-1c regulation in the liver by inhibiting the proteolytic activation of SREBP-1c during fasting. To test our hypothesis, we analyzed the hepatic SREBP-1c regulation in Adipocyte-specific ATGL knockout (AAKO) or ATGL liver-specific knockout mice (ALKO).