ANGPTL3（angiopoietin-like protein 3）是一種由肝臟和腸道分泌的蛋白質(zhì)，能夠調(diào)節(jié)脂質(zhì)代謝和胰島素敏感性。近年來(lái)，關(guān)于ANGPTL3的研究得到了越來(lái)越多的關(guān)注。

Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism. Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake. Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity; the function seems to be specific for the feeding conditions. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1. Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids; the cleaved N-terminal domain is more efficient than the uncleaved proprotein. Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol. Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT. Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR. May stimulate hypothalamic LPL activity.; Involved in angiogenesis. Binds to endothelial cells via integrin alpha-V/beta-3 (ITGAV:ITGB3), activates FAK, MAPK and Akt signaling pathways and induces cell adhesion and cell migration. May increase the motility of podocytes. Secreted from podocytes, may modulate properties of glomerular endothelial cells involving integrin alpha-V/beta-3 and Akt signaling. May induce actin filament rearrangements in podocytes implicating integrin alpha-V/beta-3 and Rac1 activation. Binds to hematopoietic stem cells (HSC) and is involved in the regulation of HSC activity probably implicating down-regulation of IKZF1/IKAROS.

1. The role of ANGPLT3 in controlling lipoprotein metabolism and risk of cardiovascular diseases is reviewed here. PMID: 29334984
2. ANGPTL8 has a functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG levels in mice in the presence of ANGPTL3 PMID: 28413163
3. The data suggests that ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice. PMID: 29104012
4. Using in vitro ketosis model by glucose starvation, studied inhibition of ketosis by momilactone B. Found momilactone B could regulate the angiopoietin-like-3 (ANGPTL3)-lipoprotein lipase (LPL)pathway, and suppressed the expression of HMGCS2 through the increased expression of STAT5b. PMID: 27874312
5. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID: 26687026
6. Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion PMID: 25954050
7. The deletion of ANGPTL3 tremendously attenuates proteinuria and protects podocytes from injury in a mouse model of adriamycin-induced nephropathy. PMID: 25710887
8. ANGPTL3 has a role in regulating white adipose tissue energy homeostasis but not in liver PMID: 26305978
9. Data indicate that expression of Angptl3 in hematopoietic stem cell (HSC) through lentiviral transduction promoted HSC expansion. PMID: 25170927
10. Angptl3 could induce actin filament rearrangement, mainly in lamellipodia formation, and that this process was mediated by integrin alpha(V)beta-mediated FAK and PI3K phosphorylation and Rac1 activation. PMID: 24294595
11. Furin has a role as the primary in vivo convertase of ANGPTL3 and endothelial lipase in hepatocytes PMID: 23918928
12. ANGPTL8, a paralog of ANGPTL3 that arose through duplication of an ancestral DOCK gene, regulates postprandial TAG and fatty acid metabolism by controlling activation of its progenitor, and perhaps other ANGPTLs PMID: 23150577
13. Angptl3, as an extrinsic factor, thus supports the stemness of hematopoietic stem cells in the bone marrow niche. PMID: 20959605
14. ANGPTL3 expression is upregulated in puromycin-induced podocyte damage and is associated with the reduction of perlecan and agrin expression PMID: 20424482
15. a molecular connection between ANGPTL3, lipoprotein lipase, and proprotein convertases PMID: 20581395
16. ANGPTL3 to be capable of regulating the motility and permeability of podocytes and that the mechanism of ANGPTL3's regulation could be associated with the altered expression of nephrin. PMID: 20633534
17. Like ANGPTL4, ANGPTL3 inhibited nonstabilized LPL but not GPIHBP1-stabilized LPL PMID: 19542565
18. ANGPTL3 stimulates endothelial cell adhesion and migration via integrin alpha vbeta 3 and induces blood vessel formation in vivo PMID: 11877390
19. affects VLDL triglyceride clearance by interfering with LPL activity PMID: 12097324
20. hepatic Angptl3 has a role in hypertriglyceridemia associated with the treatment of LXR ligand PMID: 12672813
21. the cleavage of ANGPTL3 at two sites is important for the activation of ANGPTL3 in vivo PMID: 12909640
22. Expression of ANGPTL3 was enhanced in both insulin-deficient and -resistant diabetic states; results strongly suggest ANGPTL3 to play an important role in hyperlipidemia in diabetes. PMID: 15094378
23. Elevated ANGPTL3 by leptin- or insulin-resistance is attributed to increased plasma triglycerides and free fatty acid levels in obesity. PMID: 15336575
24. Differential regulation of Angptl3 and Angptl4 by sites of expression, nutritional status, and ligands of nuclear receptors may confer unique roles of each in lipoprotein metabolism. Angptl3 is a target gene of liver X receptor PMID: 15863837
25. Angptl3-deficiecy displayed hypotriglyceridemia with elevated postheparin plasma lipoprotein lipase, with greater effect in fed state. Deficiecy in both Angptl proteins had additive effect on plasma triglycerides with survival not past 2 months of age. PMID: 16081640
26. Angptl3 acts as an inhibitor of EL and may be involved in the regulation of plasma HDL cholesterol and HDL-PL levels in humans and rodents. PMID: 17110602
27. SE1 region of ANGPTL3 and ANGPTL4 functions as a domain important for binding LPL and inhibiting its activity in vitro and in vivo. PMID: 19318355

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Secreted. Cell projection, lamellipodium.

Predominantly expressed in liver, weakly expressed in kidney and lung. Expressed in podocytes (at protein level). Expressed in hypothalamic neurons (at protein level). Expressed in bone marrow sinusoidal endothelial cells (at protein level).

KEGG: mmu:30924

STRING: 10090.ENSMUSP00000030280

UniGene: Mm.28341