Regulation of lipid metabolism by angiopoietin-like proteins

  title={Regulation of lipid metabolism by angiopoietin-like proteins},
  author={Wieneke Dijk and Sander Kersten},
  journal={Current Opinion in Lipidology},
Purpose of review The angiopoietin-like proteins (ANGPTLs) 3, 4 and 8 have emerged as key regulators of plasma lipid metabolism by serving as potent inhibitors of the enzyme lipoprotein lipase (LPL). In this review, we provide an integrated picture of the role of ANGPTL3, ANGPTL4 and ANGPTL8 in lipid metabolism by focusing on their impact on LPL activity and plasma triglyceride clearance during physiological conditions such as fasting, refeeding, exercise and cold exposure. Recent findings Upon… 

Potential Role of ANGPTL4 in the Cross Talk between Metabolism and Cancer through PPAR Signaling Pathway

The potential role of ANGPTL4 in mediating the cross talk between metabolic syndromes, such as diabetes and obesity, and cancer through regulation of its expression by PPARs is discussed.

ANGPTL4: a multifunctional protein involved in metabolism and vascular homeostasis.

The fundamental roles of Angiopoetin-like 4 in regulating metabolic and nonmetabolic functions and their implication in lipid metabolism and with several aspects of vascular function and dysfunction are summarized.

New insights into angiopoietin-like proteins in lipid metabolism and cardiovascular disease risk

    S. Kersten
    Current opinion in lipidology
  • 2019
Large-scale genetic studies provide strong rationale for continued research efforts to pharmacologically inactivate ANGPTL3 and possibly Angiopoietin-like proteins to reduce plasma lipids and coronary artery disease risk.

Regulation of angiopoietin-like protein 8 expression under different nutritional and metabolic status.

Findings may provide new options for the diagnosis and treatment of diabetes, metabolic syndromes and other diseases as the differential expression of ANGPTL8 responding to different nutritional and metabolic status during the regulation of LPL activity was reviewed.

GPIHBP1 and ANGPTL4 Utilize Protein Disorder to Orchestrate Order in Plasma Triglyceride Metabolism and Regulate Compartmentalization of LPL Activity

Recent advances in the biology and biochemistry of crucial proteins for intravascular lipolysis include solving the crystal structure of LPL, showing LPL is catalytically active as a monomer rather than as a homodimer, and that the borderline stability of Lpl’s hydrolase domain is crucial for the regulation of L PL activity.

Angiopoietin-like 4 promotes intracellular degradation of lipoprotein lipase in adipocytes

It is concluded that ANGPTL4 promotes loss of intracellular LPL by stimulating LPL degradation after LPL processing in the ER.

Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice

The mechanistic study using primary hepatocytes showed that the Angptl8 expression could be induced by insulin treatment in a dose- and time-dependent manner and suggested that GNMT might be involved in insulin-induced AngptL8 expression in HFD-mediated metabolic syndrome.

Regulation of triglyceride metabolism by Angiopoietin-like proteins.

Hepatic ANGPTL3 regulates adipose tissue energy homeostasis

Angiopoietin-like protein 3 (ANGPTL3) plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissues) in the fed state.

Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes.

Angiopoietin-like 4 (Angptl4) Protein Is a Physiological Mediator of Intracellular Lipolysis in Murine Adipocytes*

It is shown that Angptl4 is a glucocorticoid-responsive mediator of fasting-induced intracellular lipolysis and stimulates cAMP signaling in adipocytes and was restored by treatment with purified human ANGPTL4.

Linking nutritional regulation of Angptl4, Gpihbp1, and Lmf1 to lipoprotein lipase activity in rodent adipose tissue

This study demonstrates directly that ANGPTL4 is necessary for rapid modulation of LPL activity in adipose tissue and the plasticity of the LPL system is severely blunted or completely lost in insulin resistant rats.

Angptl4 Upregulates Cholesterol Synthesis in Liver via Inhibition of LPL- and HL-Dependent Hepatic Cholesterol Uptake

The hypertriglyceridemic effect of Angptl4 is attributable to inhibition of LPL-dependent VLDL lipolysis by converting LPL dimers to monomers, and AngPTl4 upregulates cholesterol synthesis in liver secondary to inhibitionof L PL- and HL-dependent hepatic cholesterol uptake.

Regulation of lipoprotein lipase by Angptl4

Atypical angiopoietin-like protein that regulates ANGPTL3

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.

Angiopoietin-Like Protein3 Regulates Plasma HDL Cholesterol Through Suppression of Endothelial Lipase

It is found that plasma ANGPTL3 levels significantly correlated with plasma HDL cholesterol and HDL-PL levels in human subjects and post-heparin plasma in Angptl3-knockout mice had higher phospholipase activity than did that in wild-type mice, suggesting that the activity of endogenous EL is elevated in Angpton-deficient mice.

The Fasting-induced Adipose Factor/Angiopoietin-like Protein 4 Is Physically Associated with Lipoproteins and Governs Plasma Lipid Levels and Adiposity*

The composite data suggest that via physical association with plasma lipoproteins, FIAF acts as a powerful signal from fat and other tissues to prevent fat storage and stimulate fat mobilization.