{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Angiopoietin‐like protein 8 (ANGPTL8), also known as betatrophin, lipasin, or RIFL, is a nutritionally regulated secreted factor produced predominantly by the liver and adipose tissue that plays a central role in lipid metabolism. Its expression is markedly induced upon feeding and suppressed by fasting, thereby coupling nutrient availability with circulating triglyceride levels (for example."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " ANGPTL8 functions primarily through formation of protein complexes—with ANGPTL3 and, in some contexts, with ANGPTL4—to inhibit lipoprotein lipase (LPL). This interaction leads to decreased LPL activity in tissues such as cardiac and skeletal muscle, thereby redistributing postprandial triglyceride‐rich lipoproteins toward adipose tissue for storage (for example."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Although early studies suggested a potential role for ANGPTL8 in stimulating pancreatic β‐cell proliferation, subsequent investigations in both knockout and overexpression models have demonstrated that its primary in vivo function is related to lipid rather than glucose homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, circulating levels of ANGPTL8 are altered in several metabolic disorders—including obesity, type 2 diabetes, non‐alcoholic fatty liver disease, and even hypertension—thereby positioning it as both a mediator and a potential biomarker of dyslipidemia and metabolic syndrome"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", among others). Recent evidence also indicates that ANGPTL8 may participate in the modulation of inflammatory signaling pathways, suggesting broader roles in cellular homeostasis. Collectively, these findings establish ANGPTL8 as a pivotal regulator of postprandial triglyceride metabolism via its dynamic interplay with other ANGPTLs, and highlight its emerging potential as a therapeutic target in dyslipidemia and associated cardiometabolic disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fabiana Quagliarini, Yan Wang, Julia Kozlitina, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1315292110"}], "href": "https://doi.org/10.1073/pnas.1315292110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24043787"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24043787"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Gang Ren, Ji Young Kim, Cynthia M Smas "}, {"type": "b", "children": [{"type": "t", "text": "Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00084.2012"}], "href": "https://doi.org/10.1152/ajpendo.00084.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22569073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22569073"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ren Zhang "}, {"type": "b", "children": [{"type": "t", "text": "The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Open Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1098/rsob.150272"}], "href": "https://doi.org/10.1098/rsob.150272"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27053679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27053679"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jorge F Haller, Ivory J Mintah, Lisa M Shihanian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride clearance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M075689"}], "href": "https://doi.org/10.1194/jlr.M075689"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28413163"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28413163"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Viktoria Gusarova, Corey A Alexa, Erqian Na, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ANGPTL8/betatrophin does not control pancreatic beta cell expansion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.09.027"}], "href": "https://doi.org/10.1016/j.cell.2014.09.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25417115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25417115"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhiyao Fu, Feven Berhane, Alemu Fite, et al. 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