Key result
ANGPTL4, ANGPTL3, and ANGPTL8 regulate lipoprotein lipase activity and compartmentalization by impacting its inherent protein instability at normal body temperature.
Why the study?
Increasing the longevity of LPL activity by attenuating inhibition from ANGPTL3, 4, and 8 is an emerging therapeutic strategy for lowering plasma triglycerides, warranting review of recent insights into ANGPTL regulation of LPL with emphasis on ANGPTL4.
Answers are grounded in this paper and cite their sources.
Understanding the posttranslational regulation of LPL by ANGPTLs provides a molecular basis for emerging therapeutic strategies aimed at lowering plasma triglyceride levels.
PURPOSE OF REVIEW: Lipoprotein lipase (LPL) is the rate-limiting enzyme for intravascular processing of circulating triglyceride-rich lipoproteins (TRLs). One emerging strategy for therapeutic lowering of plasma triglyceride levels aims at increasing the longevity of LPL activity by attenuating its inhibition from angiopoietin-like proteins (ANGPTL) 3, 4 and 8. This mini-review focuses on recent insights into the molecular mechanisms underpinning the regulation of LPL activity in the intravascular unit by ANGPTLs with special emphasis on ANGPTL4. RECENT FINDINGS: Our knowledge on the molecular interplays between LPL, its endothelial transporter GPIHBP1, and its inhibitor(s) ANGPTL4, ANGPTL3 and ANGPTL8 have advanced considerably in the last 2 years and provides an outlined on how these proteins regulate the activity and compartmentalization of LPL. A decisive determinant instigating this control is the inherent protein instability of LPL at normal body temperature, a property that is reciprocally impacted by the binding of GPIHBP1 and ANGPTLs. Additional layers in this complex LPL regulation is provided by the different modulation of ANGPTL4 and ANGPTL3 activities by ANGPTL8 and the inhibition of ANGPTL3/8 complexes by apolipoprotein A5 (APOA5). SUMMARY: Posttranslational regulation of LPL activity in the intravascular space is essential for the differential partitioning of TRLs across tissues and their lipolytic processing in response to nutritional cues.
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A 2021 study conducted a review in Regulation of intravascular lipolysis. ANGPTL4 was evaluated. ANGPTL4, ANGPTL3, and ANGPTL8 regulate lipoprotein lipase activity and compartmentalization by impacting its inherent protein instability at normal body temperature.
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