Characterisation of adipose-specific partial deletion of hormone-sensitive lipase during obesity

Abstract

Obesity is a global pandemic, and the rate of mortality due to associated pathologies, such as type 2 diabetes (T2D), is increasing every year. One of the most substantiated causes of obesity-induced T2D concerns the high amount of fatty acids (FA) delivered in the blood by a hypertrophic adipocyte. FA do not oxidize and therefore are accumulated in non-adipose organs, leading to insulin resistance (IR) (Large et al. 1998). Therefore, the study of lipid metabolism- related enzymes becomes increasingly important. Among them the lipolytic pathway and notably hormone-sensitive lipase (HSL), is the cornerstone of functional fat cell maintenance (Girousse et al. 2013). We attempted to advance in the development of a new mouse model characterized by a lipid specific HSL happloinsufficiency it order to progress in the study of this lipase. We have validated the model by obtaining mice with nearly half deletion of HSL specific to adipose tissues. Nevertheless, the tolerance tests results do not show noticeable differences between control and study group. Such genetic modification do not seem to have systemic metabolic effects.