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H2020Individual fellowship2017–2020

TGDNL · Mechanisms of cellular fatty acid homeostasis

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-08-01 → 2020-07-31
EU contribution
€265,059
Participants
2
Scheme
MSCA-IF-GF

Lines connect the coordinator with its partners.

Results in brief

Mechanisms of cellular fatty acid homeostasis

In life, access to metabolic energy fluctuates. Our cells have therefore developed the ability to store energy, predominantly as fat (triglycerides) in organelles known as lipid droplets (LDs). Although the capacity to store triglycerides is key for survival when access to nutrients is limited, increased energy intake combined with decreased energy utilization has led to a global increase in multiple metabolic diseases, e.g. obesity and non-alcoholic fatty liver disease, in today’s society. The overarching objective of this project is to determine how cells regulate and coordinate lipid storage processes in order to achieve energy homeostasis. The results generated may therefore uncover novel mechanisms controlling cellular lipid homeostasis and provide new therapeutic avenues to treat diseases characterized by overwhelming the storage capacity of cells.

Data: CORDIS, © European Union

Project objective

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.

Original text from CORDIS.

Participants

  • KAROLINSKA INSTITUTET · STOCKHOLMCoordinatorSweden
  • PRESIDENT AND FELLOWS OF HARVARD COLLEGE · CambridgeUnited States

Links

Data: CORDIS, © European Union