Lipoprotein lipase hydrolysis products are associated with Akt signalling in THP-1 macrophages

Lipoprotein lipase (LPL) is an extracellular enzyme responsible for the hydrolysis of lipids from circulating lipoproteins for delivery to other tissues in the body. It has been shown to be highly expressed in atherosclerotic lesions - locations within the vasculature that display increased lipid deposition, inflammation, and tissue damage, and it is implicated in the progression of disease. The mechanisms behind this, however, are not fully understood.

Our laboratory has previously shown that the products of LPL hydrolysis of human total lipoproteins activate various signalling molecules and receptor tyrosine kinases in THP-1 human macrophages. Of particular interest is Akt (or protein kinase B), which was found to be activated by a free fatty acid (FFA) sub-component of the LPL hydrolysis products. Akt is part of the phosphoinositide 3-kinase (PI3K) signalling pathway, and it plays a role in various cell processes, such as cell survival, protein synthesis, and insulin signalling. We hypothesize that Akt activation may play a role in cellular lipid accumulation in macrophages.
Studies to date have attempted to isolate the FFA that influences Akt activation, as well as to evaluate parameters such as activation time and dose effects. We have found a dose-dependent effect of FFA treatment on Akt activation, and we have narrowed down the class of FFA responsible for activation.