Key result
ANGPTL8 regulates lipoprotein metabolism and links to cardiometabolic disorders despite unclear direct pathogenicity.
Why the study?
Whether ANGPTL8 has a direct pathogenic role in cardiometabolic diseases beyond its role in lipoprotein metabolism remains to be explored.
Understanding the diverse functions of ANGPTL8 may unveil new therapeutic opportunities for cardiometabolic disorders.
Should not yet change cardiometabolic management; leaves open ANGPTL8 as a therapeutic target for targeted trials.
Angiopoietin-like protein (ANGPTL) family members, mainly ANGPTL3, ANGPTL4 and ANGPTL8, are physiological inhibitors of lipoprotein lipase (LPL), and play a critical role in lipoprotein and triglyceride metabolism in response to nutritional cues. ANGPTL8 has been described by different names in various studies and has been ascribed various functions at the systemic and cellular levels. Circulating ANGPTL8 originates mainly from the liver and to a smaller extent from adipose tissues. In the blood, ANGPTL8 forms a complex with ANGPTL3 or ANGPTL4 to inhibit LPL in fed or fasted conditions, respectively. Evidence is emerging for additional intracellular and receptor-mediated functions of ANGPTL8, with implications in NFκB mediated inflammation, autophagy, adipogenesis, intra-cellular lipolysis and regulation of circadian clock. Elevated levels of plasma ANGPTL8 are associated with metabolic syndrome, type 2 diabetes, atherosclerosis, hypertension and NAFLD/NASH, even though the precise relationship is not known. Whether ANGPTL8 has direct pathogenic role in these diseases, remains to be explored. In this review, we develop a balanced view on the proposed association of this protein in the regulation of several pathophysiological processes. We also discuss the well-established functions of ANGPTL8 in lipoprotein metabolism in conjunction with the emerging novel extracellular and intracellular roles of ANGPTL8 and the implicated metabolic and signalling pathways. Understanding the diverse functions of ANGPTL8 in various tissues and metabolic states should unveil new opportunities of therapeutic intervention for cardiometabolic disorders.
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Abu‐Farha et al. (2020) conducted a review in Cardiometabolic disorders. ANGPTL8 was evaluated. ANGPTL8 regulates lipoprotein metabolism and has emerging intracellular roles implicated in inflammation, autophagy, and cardiometabolic disorders, though its direct pathogenic role remains unclear.
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