The role of ABHD13 in brain lipid metabolism

Lipids play an essential role in the regulation of various physiological processes such as membrane synthesis, energy storage and signal transduction. Therefore, lipid synthesis and degradation must be tightly regulated, and imbalances are often associated with lipid-associated diseases. Proteins containing a so-called alpha/beta hydrolase domain fold (ABHDs) play key roles in physiological processes, and some ABHD proteins have been linked to genetic disorders in humans. Enzymes of this family exhibit various enzymatic activities, including protease, esterase, lipase, and amidase activity. While some members of the ABHD family are well studied, others are poorly characterized, and the physiological substrates and biological functions of several ABHDs remain to be investigated. One of these enzymes is ABHD13, an uncharacterized serine hydrolase. Our preliminary data indicate that the enzyme hydrolyzes various lipids, including those with signaling function. Mice with a systemic deletion of ABHD13 (ABHD13-ko), are fertile and exhibit normal growth and weight. However, ABHD13-ko mice exhibit alterations in the brain, and further analysis indicates behavioral abnormalities. The main goal of this project is to decipher the physiological function of ABHD13 and elucidate the mechanisms causative for the altered behavior of ABHD13-ko-mice. Based on our preliminary observations, we hypothesize that ABHD13 plays an important role in phospholipid metabolism in the brain, thereby affecting brain development and neuronal function. Since ABHD13 is a poorly characterized enzyme, we expect that our experiments will provide new insights into brain lipid metabolism and may reveal metabolic relationships necessary for understanding the pathogenesis of genetic or acquired neuronal disorders.