LPL is produced by many tissues such as adipose tissue, heart, skeletal muscle, islets and macrophages, where it is anchored to the cell surface exterior via heparan sulfate proteoglycans (Mulder et al., 1992; Sendak and Bensadoun, 1998; Wang and Eckel, 2009). Patients with a genetic mutation in either LPL gene or apoC-II, a specific cofactor for LPL, suffer from hypertriglyceridemia as well as massive hyperchylomicronemia (Wang and Eckel, 2009). LPL activity in different tissues is regulated by mechanisms that are tissue specific, in response to nutritional status and helps in the cellular FFA uptake in these tissues. During fasting, LPL activity is the highest in the oxidative tissues such as skeletal and heart muscles directing FFA from circulating TG towards oxidation. In the fed condition, LPL activity decreases in oxidative tissue and increases in white adipose tissue, thus promoting energy storage (Kersten, 2014; Wang and Eckel, 2009).
Hormonal regulation of LPL also in general follows an inverse relationship between skeletal muscle and adipose tissue. Thus, insulin and thyroid hormone increase the expression of LPL in adipose while reducing that in skeletal muscle, whereas estrogens, testosterone and catecholamines have reverse effects in these tissues (Wang and Eckel, 2009). LPL-interacting proteins LPL activity is modulated by several interacting proteins, including lipase maturation factor 1 (LMF1), glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), receptor-associated protein (RAP), apolipoprotein A5 (ApoA5), and ANGPTLs 3, 4 and 8 (reviewed recently by Kersten, 2017). LMF1 is an ER resident membrane bound protein, which is needed for proper post-translational maturation and thus activity of LPL protein. Indeed, mutations in LMF1 result in severe hypertriglyceridemia (Wang and Eckel, 2009).
The transport of LPL to its site of action at the luminal surface of capillary endothelium