New research published in Nature Microbiology has shed light on the molecular process behind the weight loss experienced by individuals infected with the Trypanosoma brucei parasite, the causative agent of African sleeping sickness. This progressive wasting disease is characterized by the rapid growth of the parasite in adipose tissue (AT), which leads to significant weight loss.
The study focused on understanding the disturbance in the balance between lipogenesis and lipolysis within adipocytes during African sleeping sickness. Lipogenesis refers to the synthesis of fat molecules, while lipolysis refers to the breakdown of fats.
The researchers found that increased lipolysis occurs during infection, resulting in the degradation of triacylglycerol (TAG) into diacylglycerol and monoacylglycerol. These molecules are then released into the interstitial spaces of AT and eventually into the circulatory system as glycerol and free fatty acids (FFAs). This process is regulated by inflammatory molecules, sympathetic factors, hormones, and bacterial products.
To investigate the role of lipolysis in weight loss during African sleeping sickness, the researchers infected mice with the T. brucei parasite. They observed progressive weight loss in the mice’s gonadal AT, as well as a reduction in adipocyte lipid droplet area. The release of FFAs and glycerol increased initially but eventually decreased, possibly due to the depletion of lipid stores and immune infiltration.
Furthermore, the researchers discovered that the induction of sympathetic tone or fasting and re-feeding did not contribute significantly to adipocyte lipolysis during T. brucei infection. In contrast, mice lacking the adipose triglyceride lipase (ATGL) enzyme, which is responsible for lipolysis, exhibited lower secretion of FFAs and glycerol when infected with the parasite. This suggests that ATGL is essential for the increased rates of lipolysis observed during African sleeping sickness.
The study also identified specific changes in the composition of FFAs in the interstitial AT space during T. brucei infection. Certain FFAs, such as C18:2, were found to be selectively toxic to the parasite.
In conclusion, the research highlights the role of lipolysis and the ATGL enzyme in the weight loss associated with African sleeping sickness. While further studies are needed to understand the role of glycerol and the physiological implications of lipolysis during this infection, these findings provide valuable insights into the mechanisms behind the disease-induced wasting syndrome.
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