Increased Serum Angiopoietin-Like 6 Ahead of Metabolic Syndrome in a Prospective Cohort Study

Abstract

Background Despite being an anti-obesity hepatokine, the levels of serum angiopoietin-like 6 (ANGPTL6) are elevated in various metabolic diseases. Thus, ANGPTL6 expression may reflect metabolic burden and may have compensatory roles. This study investigated the association between serum ANGPTL6 levels and new-onset metabolic syndrome. Methods In total, 221 participants without metabolic syndrome were randomly selected from a rural cohort in Korea. Baseline serum ANGPTL6 levels were measured using an enzyme-linked immunosorbent assay. Anthropometric and biochemical markers were analyzed before and after follow-up examinations. Results During an average follow-up period of 2.75 (interquartile range, 0.76) years, 82 participants (37.1%) presented new-onset metabolic syndrome and had higher ANGPTL6 levels before onset than those without metabolic syndrome (48.03±18.84 ng/mL vs. 64.75±43.35 ng/mL, P =0.001). In the multivariable adjusted models, the odds ratio for the development of metabolic syndrome in the highest quartile of ANGPTL6 levels was 3.61 (95% confidence interval, 1.27 to 10.26). The use of ANGPTL6 levels in addition to the conventional components improved the prediction of new-onset metabolic syndrome (area under the receiver operating characteristic curve: 0.775 vs. 0.807, P =0.036). Conclusion Increased serum ANGPTL6 levels precede the development of metabolic syndrome and its components, including low high density lipoprotein, high triglyceride, and high glucose levels, which have an independent predictive value for metabolic syndrome.

Response: Increased Serum Angiopoietin-Like 6 Ahead of Metabolic Syndrome in a Prospective Cohort Study (Diabetes Metab J 2019;43:521-9)

“…Previously, we confirmed in mouse models that serum ANGPTL6 levels were increased by high fat diet and attenuated by exercise training [6]. Based on this, we interpreted our results in a prospective cohort study that upregulation of ANGPTL6 is a protective response alleviating metabolic stress [1]. We suggest that increased serum ANGPTL6 levels in a preclinical status reflect the increase in ongoing metabolic stress; thus, it could be used as a predictable biomarker of development of metabolic syndrome.…”

“…We really appreciate Dr. Kim for expressing interest and providing valuable comments on our recently published article, “Increased serum angiopoietin-like 6 ahead of metabolic syndrome in a prospective cohort study” which was published in Diabetes & Metabolism Journal [1].…”

Effects of Exercise Intervention on Mitochondrial Stress Biomarkers in Metabolic Syndrome Patients: A Randomized Controlled Trial

“…Thus, our baseline data are consistent with the evidence from previous clinical studies showing that each of the three biomarkers are markedly elevated in MetS patients [ 17 , 25 , 29 ]. Furthermore, possessing potential as independent predictors of new-onset MetS, these stress markers may be useful in the screening and prediction of individuals at high risk of acquiring metabolic disorders, and in making early intervention decisions during pre-clinical stages [ 30 , 31 ].…”

“…Among them, ANGPTL6 is regarded as a metabolically beneficial hepatokine since it exerts anti-obesogenic and insulin-sensitizing effects [ 15 ]. However, paradoxically, elevated serum ANGPTL6 concentrations have been found prior to MetS onset (in a prospective cohort study) in addition to being found in MetS patients (a cross-sectional study) [ 17 , 31 ]. Hence, we have suggested that circulating ANGPTL6 levels have a strong predictive potential and diagnostic value for MetS.…”

Letter: Increased Serum Angiopoietin-Like 6 Ahead of Metabolic Syndrome in a Prospective Cohort Study (Diabetes Metab J 2019;43:521-9)

“…In this article entitled “Increased serum angiopoietin-like 6 ahead of metabolic syndrome in a prospective cohort study,” Namkung et al [10] prospectively evaluated the association between serum ANGPTL6 level and new-onset metabolic syndrome in a rural cohort in Korea. They showed that serum ANGPTL6 level was already significantly elevated before developing new-onset metabolic syndrome, which has an independent predictive value for metabolic syndrome.…”