ANGPTL4 Specific Neutra™ Antibody Products

Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that regulates lipid metabolism and energy balance. ANGPTL4 is expressed in various tissues, including adipose tissue, liver, and muscle, and its expression is modulated by factors like fasting, hypoxia, and peroxisome proliferator-activated receptors (PPARs). ANGPTL4 is composed of a fibrinogen-like C-terminal domain and a coiled-coil N-terminal domain. As an important regulator of lipid metabolism, ANGPTL4 influences processes such as lipolysis, fatty acid oxidation, and triglyceride clearance, making it a key player in metabolic homeostasis. It has been proved that ANGPTL4 neutralizing antibodies attenuated the pancreatitis-related symptoms in mice.

Its Gene ID: 51129, UniProtKB ID: Q9BY76, and OMIM ID: 605910.

ANGPTL4 Signaling Pathways

The signaling pathways involving ANGPTL4 are complex and multifaceted. ANGPTL4 is known to modulate various signaling cascades, including the AMPK pathway, PPAR pathway, NF-κB pathway and Wnt/β-catenin signaling. ANGPTL4 can activate AMPK, a key regulator of cellular energy homeostasis, leading to increased fatty acid oxidation and decreased lipid synthesis. It also interacts with PPARs, which are critical in lipid metabolism and inflammation. ANGPTL4 can also stimulate NF-κB signaling, promoting inflammatory responses and affecting various cellular processes. Additionally, ANGPTL4 acts as a Wnt signaling antagonist by binding to syndecans and forming a ternary complex with the Wnt co-receptor LRP6, resulting in reduced signaling.

Fig.1 The role of ANGPTL4 as an endogenous inhibitor of lipoprotein lipase and its regulation.¹

The Multifaceted Roles of ANGPTL4

ANGPTL4 can promote cancer progression by enhancing tumor angiogenesis, metastasis, and tumor cell survival through interactions with integrins and extracellular matrix components. In inflammation, ANGPTL4 modulates immune responses by regulating macrophage polarization and cytokine production. ANGPTL4 also functions as a matricellular protein to stimulate angiogenesis and extracellular matrix remodeling, facilitating tissue repair. In kidney disease, ANGPTL4 is implicated in the pathogenesis of proteinuric kidney diseases by affecting podocyte function and renal lipid metabolism. In addition, ANGPTL4 plays an important role in energy homeostasis, cell differentiation and other physiological and pathological processes.

Fig.2 Roles of ANGPTL4.²

Antibodies Targeting ANGPTL4

By specifically binding to ANGPTL4 and inhibiting its activity, neutralizing antibodies can potentially modulate lipid metabolism, glucose homeostasis, and inflammation. In conditions like obesity, dyslipidemia, and type 2 diabetes where ANGPTL4 dysregulation plays a role, a neutralizing antibody could help restore metabolic balance and improve clinical outcomes. Studies have shown neutralizing antibody-mediated inhibition of Angptl4 leads to plasma triglyceride levels and modestly lower serum cholesterol levels. There is other research evidence indicating therapy with anti-ANGPTL4 neutralizing antibodies greatly expedited pulmonary recovery and enhanced lung tissue integrity, while also reducing pulmonary edema and damage in secondary pneumococcal pneumonia. In cancer, inhibiting ANGPTL4 with a neutralizing antibody may hinder tumor progression by impeding angiogenesis and metastasis. Treatment with anti-cANGPTL4 mAb in mouse mode has been demonstrated to significantly retard melanoma growth. ANGPTL4-targeting neutralizing antibodies hold promise as a therapeutic strategy for various diseases.

Fig.3 A proposed mechanism for ANGPTL4-mediated melanoma malignancy progression.³

Creative Biolabs offers more than twenty different types of anti-ANGPTL4 antibody products. These antibodies are recombinantly expressed and have a variety of applications to meet your diverse research needs.

REFERENCES

1. From Wikimedia: By Sander kersten - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Overview_ANGPTL4.png
2. Tong, Zhoujie, et al. "Cross-talk between ANGPTL4 gene SNP Rs1044250 and weight management is a risk factor of metabolic syndrome." Journal of Translational Medicine 19 (2021): 1-12.
3. Izraely, Sivan, et al. "ANGPTL4 promotes the progression of cutaneous melanoma to brain metastasis." Oncotarget 8.44 (2017): 75778.