Regulation of ANGPTL4 and its skeletal actions
Abstract
Angiopoietin-like protein 4 (ANGPTL4) is a glycoprotein secreted mainly from adipose and liver tissue. ANGPTL4 is an inhibitor of the enzyme lipoprotein lipase, which catalyzes the hydrolysis of triglyceride. In addition to the full-length protein, two proteolytic cleavage products of ANGPTL4 can be found: the N-terminal coiled-coil domain (CCD) and the C-terminal fibrinogen-like domain (FLD). A number of physiological functions have been described for ANGPTL4, including the regulation of lipid metabolism, glucose homeostasis and angiogenesis. The expression of ANGPTL is induced by fasting and by increased levels of free fatty acids, generally through the activation of peroxisome proliferator-activated receptors (PPARs) signaling. Thus, ANGPTL4 plays a central role in the response to changes in lipid availability and the body’s energy demands.
So far, only a small number of studies investigated the skeletal effects of ANGPTL4. It was found that CCD potently inhibits osteoclast formation and activity, suggesting a novel linkage between adipose tissue and bone. Other studies focused on the skeletal activity of ANGPTL4 under inflammatory conditions and the role of ANGPTL4 in hypoxic regions, for example in cells population within the synovium of patients with rheumatoid arthritis and in the callus that forms at fracture sites. Results from in vitro studies in bone cells, animal models, and investigations in human skeletal tissues are not entirely congruent and a clear understanding of the role of ANGPTL4 in skeleton is still missing.Keywords
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DOI: http://dx.doi.org/10.18103/imr.v3i1.256
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