Lysosomal acid lipase (LAL) promoted endothelial proliferation in cold-activated adipose tissue, according to a new study published in Adipocyte.

The authors of the study recently observed that capillary endothelial cells in thermogenic adipose tissue absorb and metabolize entire triglyceride-rich lipoprotein (TRL) particles in the presence of cold exposure. This process is dependent on lipoprotein lipase (LPL), LAL, and the cluster of differentiation 36 (CD36).

In patients with lysosomal acid lipase deficiency (LAL-D), the loss of LAL in the endothelial cells causes impairment in endothelial proliferation and the diminishing of thermogenesis adaptation.

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Cell culture experiments demonstrate that LAL-mediated TRL processing generates reactive oxygen species, which then activates hypoxia-induced factor-mediated proliferative pathways.

“In the current manuscript, we provide in vivo evidence that LAL-deficiency impairs proliferation of endothelial cells in thermogenic adipose tissue,” the authors wrote.

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This is in response to the question leftover from their previously published paper on whether LAL-mediated TRL-processing in endothelial cells is relevant in vivo. They then completed this study by investigating endothelial cell proliferation during cold exposure in mice lacking LAL in their endothelial cells.

The results from this experiment confirmed their previously published data that LAL-mediated TRL processing is needed for normal cold-induced endothelial proliferation. However, researchers are still not certain about the association between endothelial proliferation and increased thermogenic recruitment.

“Given that the uptake of entire TRL particles in brown adipose tissue / white adipose tissue depends on LPL and CD36, it appeared likely that similar pathways might also be present in the skeletal and cardiac muscles,” the researchers concluded.

Further studies involving physical exercise in cardiac impairment models may help us better understand the role of TRL processing by endothelial LAL in cardiac muscle function.


Fischer AW, Jaeckstein MY, Heeren J. Lysosomal acid lipase promotes endothelial proliferation in cold-activated adipose tissueAdipocyte. Published online December 25, 2021. doi:10.1080/21623945.2021.2013416