Lipolysis

 

The breakdown of fat, or lipolysis, is a dynamic and tightly controlled process that allows us to maintain balanced energy levels during periods of energy fluctuations. For example, during periods of energy deficit, such as during starvation or prolonged exercise, lipolysis is activated to replenish energy stores. Conversely, during periods of energy excess, such as following the consumption of a carbohydrate rich meal, lipolysis is inhibited by insulin. Regulation of lipolysis is thus of immense importance and when perturbed, it can lead to the development of metabolic disorders such as type 2 diabetes and non-alcoholic fatty liver disease.

Despite this, the mechanism by which insulin regulates lipolysis remains controversial. The current working model focuses on the cAMP degrading function of a protein called phosphodiesterase 3B (PDE3B) in explaining this process. However, due to several studies providing evidence that whilst PDE3B is essential, its function is not, further investigation is needed to elucidate this process.

Our lab has shown that another protein called abhydrolase domain containing 15 (ABHD15), is also important in insulin-mediated lipolysis inhibition. We have found that when ABHD15 levels are reduced or ablated in fat cells, insulin can no longer inhibit lipolysis, but that this effect can be rescued upon ABHD15 re-expression.

Through a comprehensive interdisciplinary study comprising cell biology, mass spectrometry and animal metabolism we hope to clarify controversies about the process and shed light on ABHD15’s role in insulin’s inhibition of lipolysis.

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adipocytes from WT and ABHD15 KO cells