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Serum Level of ANGPTL6 in Metabolic Syndrome And its Up‐ And Downstream Targets
Author(s) -
YEH Byung Il,
NAMKUNG JUN
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.884.23
Subject(s) - metabolic syndrome , medicine , endocrinology , receptor , gluconeogenesis , nuclear receptor , diabetes mellitus , transfection , biology , lipid metabolism , downregulation and upregulation , metabolism , biochemistry , gene , transcription factor
One of novel hepatocytokines, angiopoietin‐like 6 (ANGPTL6) showed therapeutic potential against diabetes and obesity in animal model by increased energy expenditure, decreased gluconeogenesis, and improved lipid and sugar profiles. However, human studies demonstrated paradoxically increased serum ANGPTL6 levels in preeclampsia and diabetes. We analyzed serum levels of ANGPTL6 in Korean persons. Serum ANGPTL6 levels were significantly higher in subjects with metabolic syndrome than those in the healthy group, and in women than in men. Among the components of metabolic syndrome, subjects with decreased high‐density lipoprotein cholesterol had significantly increased serum ANGPTL6. Metabolic syndrome itself and waist circumference could be used, in addition to sex and age, as independent predictors of serum ANGPTL6 level. To identify functions of human ANGPTL6, expressional profiling by ANGPTL6 treatment to human hepatoma cell HUH7 was performed. Among targets of rate‐limiting or key enzymes of major metabolism, expression of glucose‐6‐phosphatase was decreased by ANGPTL6 transfection and increased by ANGPTL6 siRNA transfection. With computational prediction, several nuclear receptor response elements were discovered in the promoter region of ANGPTL6. In vitro assay showed increased ANGPTL6 expression after farnesoid X receptor and liver X receptor. In conclusion, human ANGPTL6, which decreases gluconeogenesis in human hepatocytes, seems to be compensatory up‐regulated or resistant status in metabolic syndrome. As expression of ANGPTL6 can be up‐regulated by nuclear receptor agonists, therapeutic potentials against metabolic syndrome exist also in human.