ArticleProceedings of the National Academy of Sciences of the United States of America2012
Atypical angiopoietin-like protein that regulates ANGPTL3.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02812888 (Serum Betatrophin Levels and Its Influencing Factors in Patients With Hyperthyroidism), which is not on this map. Cited by 253 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Serum Betatrophin Levels and Its Influencing Factors in Patients With Hyperthyroidism
Who cites it
253 citing papers in PubMed, 2 syntheses or guidelines pooled it, 452 citations in OpenAlex.
- The Relationship between Circulating ANGPTL8/Betatrophin Concentrations and Adult Obesity: A Meta-Analysis.Disease markers · 2019Pooled it
- Circulating Betatrophin Levels and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.PloS one · 2017Pooled it
- Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.Diabetes, obesity & metabolism · 2025Trial
- Effect of physical activity in a weight loss program on circulating total ANGPTL8 concentrations in northern Americans with obesity: A prospective randomized controlled trial.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2022Trial
- Association between angiopoietin-like protein 2 and lectin-like oxidized low-density lipoprotein receptor 1 ligand containing apolipoprotein B in patients with type 2 diabetes.The Journal of international medical research · 2018Trial
- Circulating ANGPTL8/Betatrophin Concentrations Are Increased After Surgically Induced Weight Loss, but Not After Diet-Induced Weight Loss.Obesity surgery · 2016Trial
- The Angiopoietin-like Protein (ANGPTL) Axis in Dyslipidemia: Mechanisms, Cardiovascular Risk, and Emerging Therapies.Current atherosclerosis reports · 2026Review
- Effects of fenofibrate on angiopoietin-like 3/4/8 proteins and apolipoprotein A5.Journal of lipid research · 2026Article
- Associations of ANGPTL3/4/8 proteins and complexes with heart failure and heart failure mortality.Lipids in health and disease · 2026Article
- Disruption of the angiopoietin-like system connects lipid homeostasis and hypothalamic dysfunction in ALS.BMC medicine · 2026Article
- A neutralizing APOA5 monoclonal antibody reduces amounts of lipoprotein lipase in capillaries and triggers hypertriglyceridemia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Adipokine in Metabolic Liver Disease: Adipo-Brain-Liver Cross talk.International journal of endocrinology · 2026Review
- Genomic Structural Equation Modeling Provides an Initial View of the Genetic Architecture Related to Type 1 Gaucher Disease.Human mutation · 2026Article
- Association between serum ANGPLT8 levels and atherogenic index of plasma in Chinese patients with type 2 diabetes mellitus.Frontiers in cardiovascular medicine · 2026Article
- Angiopoietin-like 3 monomers are abundant in human plasma but are unable to inhibit endothelial lipase.JCI insight · 2025Article
- ANGPTL4: A Comprehensive Review of 25 Years of Research.Cancers · 2025Review
- Sexually dimorphic effects of angiopoietin-like 2 on energy metabolism and hypothalamic neuropeptide regulation.International journal of obesity (2005) · 2025Article
- Clinical Value of Circulating Angiopoietin-like Protein 8/Betatrophin Levels in Patients with Acute Pancreatitis.Medicina (Kaunas, Lithuania) · 2025Article
- ANGPTL3/8 is an atypical unfoldase that regulates intravascular lipolysis by catalyzing unfolding of lipoprotein lipase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Chronic cold exposure reprograms feeding-regulated LPL activity in white adipose tissues through hepatic ANGPTL3 and ANGPTL8.Life metabolism · 2025Article
193 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Angiopoietin-like proteins (ANGPTLs) play major roles in the trafficking and metabolism of lipids. Inactivation of ANGPTL3, a gene located in an intron of DOCK7, results in very low levels of LDL-cholesterol (C), HDL-C and triglyceride (TAG). We identified another ANGPTL family member, ANGPTL8, which is located in the corresponding intron of DOCK6. A variant in this family member (rs2278426, R59W) was associated with lower plasma LDL-C and HDL-C levels in three populations. ANGPTL8 is expressed in liver and adipose tissue, and circulates in plasma of humans. Expression of ANGPTL8 was reduced by fasting and increased by refeeding in both mice and humans. To examine the functional relationship between the two ANGPTL family members, we expressed ANGPTL3 at physiological levels alone or together with ANGPTL8 in livers of mice. Plasma TAG level did not change in mice expressing ANGPTL3 alone, whereas coexpression with ANGPTL8 resulted in hypertriglyceridemia, despite a reduction in circulating ANGPTL3. ANGPTL8 coimmunoprecipitated with the N-terminal domain of ANGPTL3 in plasma of these mice. In cultured hepatocytes, ANGPTL8 expression increased the appearance of N-terminal ANGPTL3 in the medium, suggesting ANGPTL8 may activate ANGPTL3. Consistent with this scenario, expression of ANGPTL8 in Angptl3(-/-) mice failed to promote hypertriglyceridemia. Thus, 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. Inhibition of ANGPTL8 provides a new therapeutic strategy for reducing plasma lipoprotein levels.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.