The role of phosphatidylserine-decarboxylase for brown adipose tissue formation and function

• Applicants: Dr. Josef Ecker; Professor Dr. Martin Klingenspor; Professor Dr. Gerhard Liebisch
• Subject Area: Nutritional Sciences
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446175916

Mammalian adipose tissue can be categorized in white and brown adipose tissue (BAT). Brown adipocytes contain several small lipid droplets and can generate heat to maintain a stable body temperature by non-shivering thermogenesis, which is mediated by uncoupling protein 1 (UCP1) located in the inner mitochondrial membrane. Because substrates for BAT thermogenesis are glucose and free fatty acids, BAT is involved in systemic glucose and lipid homeostasis. Indeed, the presence and activity of human BAT correlates with higher energy expenditure, lower adiposity, and reduced risk of insulin resistance. Therefore, activation of brown adipocyte thermogenesis is considered a promising strategy to increase energy expenditure. Further, the identification of mechanisms regulating brown adipocyte development and thermogenesis might be useful to combat metabolic pathologies and diseases.We and others have previously shown that the membrane lipid composition is precisely controlled on the cellular and subcellular level, cell type-specific and adapted to cellular functions. The lipid composition of membranes significantly influences physical membrane properties including lipid packing density and fluidity. The endoplasmic reticulum (ER) is the prime organelle involved in phospholipid synthesis, followed by the Golgi apparatus and mitochondria. A significant fraction of cellular phosphatidylethanolamine (PE), a major cell membrane lipid, is generated from phosphatidylserine (PS) by phosphatidylserine-decarboxylase (PISD) in mitochondria.Because in our preliminary data PISD activity correlates with murine adipose tissue browning and UCP1-mediated respiration in brown adipocytes, we propose that PlSD is a key regulator of mitochondrial bioenergetics in BAT. Therefore, the main objectives of the proposed research program are to investigate the physiological and pathophysiological relevance of PISD for non-shivering thermogenesis in vivo as well as to identify the mechanism underlying PISD-mediated regulation of mitochondrial bioenergetics.

• DFG Programme: Research Grants