TGDNL | Mechanisms of cellular fatty acid homeostasis

Summary
The ability of cells to precisely maintain an internal steady state of lipids is essential for life. While homeostatic mechanisms controlling specific lipids such as sterols are well characterized, the regulation and coordination of fatty acid (FA) and triacylglycerol (TG) synthesis remains largely unknown. Several common metabolic disorders, including obesity and type 2 diabetes, lead to nonalcoholic fatty liver disease (NAFLD), a condition characterized by increased accumulation of hepatic TGs. Since a significant proportion of subjects with NAFLD develop potentially fatal complications, e.g. non-alcoholic steatohepatitis (NASH) and cirrhosis, it is of fundamental importance to study the mechanisms that promote hepatic lipid accumulation. By combining advanced molecular techniques with state-of-the-art clinical research, a translational approach will be applied herein to uncover how cells coordinate glycerolipid and FA synthesis. The studies focus on acyl-CoA:diacylglycerol O-transferase 2 (DGAT2), an enzyme catalysing the final step of TG biosynthesis and a drug target for NAFLD, which according to recent data may play an important role in FA synthesis regulation. The results generated in this project may uncover novel mechanisms controlling cellular lipid homeostasis and provide new therapeutic avenues to treat NAFLD and NASH.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/704647
Start date: 01-08-2017
End date: 31-07-2020
Total budget - Public funding: 265 059,00 Euro - 265 059,00 Euro
Cordis data

Original description

The ability of cells to precisely maintain an internal steady state of lipids is essential for life. While homeostatic mechanisms controlling specific lipids such as sterols are well characterized, the regulation and coordination of fatty acid (FA) and triacylglycerol (TG) synthesis remains largely unknown. Several common metabolic disorders, including obesity and type 2 diabetes, lead to nonalcoholic fatty liver disease (NAFLD), a condition characterized by increased accumulation of hepatic TGs. Since a significant proportion of subjects with NAFLD develop potentially fatal complications, e.g. non-alcoholic steatohepatitis (NASH) and cirrhosis, it is of fundamental importance to study the mechanisms that promote hepatic lipid accumulation. By combining advanced molecular techniques with state-of-the-art clinical research, a translational approach will be applied herein to uncover how cells coordinate glycerolipid and FA synthesis. The studies focus on acyl-CoA:diacylglycerol O-transferase 2 (DGAT2), an enzyme catalysing the final step of TG biosynthesis and a drug target for NAFLD, which according to recent data may play an important role in FA synthesis regulation. The results generated in this project may uncover novel mechanisms controlling cellular lipid homeostasis and provide new therapeutic avenues to treat NAFLD and NASH.

Status

CLOSED

Call topic

MSCA-IF-2015-GF

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2015
MSCA-IF-2015-GF Marie Skłodowska-Curie Individual Fellowships (IF-GF)