title: Altered Concentrations in Dyslipidemia Evidence a Role for ANGPTL8/Betatrophin in Lipid Metabolism in Humans.
abstract: Angiopoietin-like protein 8 (ANGPTL8)/betatrophin is a secreted protein initially involved in β-cell replication. Recent data in humans and mice models suggest that ANGPTL8/betatrophin is more related to lipid metabolism.
  
  
  
  The aim of the present study was to compare the circulating concentrations of ANGPTL8/betatrophin in individuals with dyslipidemia defined as having high or low levels of high-density lipoprotein (HDL)-cholesterol or triglycerides, respectively.
  
  
  
  Serum concentrations of ANGPTL8/betatrophin were measured by an ELISA in 177 subjects. We studied two different selected case-control dyslipidemic cohorts including individuals with high (n = 43) or low (n = 46) circulating concentrations of HDL-cholesterol or with low (n = 48) or high (n = 40) levels of triglycerides.
  
  
  
  Circulating concentrations of ANGPTL8/betatrophin were significantly lower in individuals with dyslipidemia (P < .001) in both males (controls 27.8 ± 15.2 vs dyslipidemic 17.0 ± 11.2 ng/mL) and females (controls 50.0 ± 22.2 vs dyslipidemic 27.0 ± 16.5 ng/mL). The magnitude of the differences was higher in dyslipidemic patients with low HDL-cholesterol than in those with high triglyceride concentrations. ANGPTL8/betatrophin levels were lower in subjects with type 2 diabetes (P < .001), but the impact of type 2 diabetes vanished (P = .257) when the effect of dyslipidemia was included in the analysis.
  
  
  
  We conclude that serum ANGPTL8/betatrophin concentrations are altered in human dyslipidemia. ANGPTL8/betatrophin emerges as a potential player in dyslipidemia with a strong association with HDL-cholesterol and a potential therapeutic tool for the treatment of dyslipidemia.
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez-Ambrosi
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Eider
authors.initials: E
authors.lastname: Pascual-Corrales
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Catalán
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ramírez
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Romero
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Vila
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ibáñez
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Margall
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Camilo
authors.initials: C
authors.lastname: Silva
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Gil
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Salvador
authors.affiliation: Metabolic Research Laboratory (J.G.-A., V.C., A.R., B.R., G.F.) and Departments of Endocrinology and Nutrition (E.P.-C., S.R., N.V., P.I., M.A.M., C.S., J.S., G.F.) and Biochemistry (M.J.G.), Clínica Universidad de Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (J.G.-A., V.C., A.R., B.R., S.R., P.I., C.S., M.J.G., J.S., G.F.), Instituto de Salud Carlos III, and Obesity and Adipobiology Group (J.G.-A., V.C., A.R., B.R., S.R., N.V., P.I., M.A.M., C.S., M.J.G., G.F.), Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
mesh_terms: D000328:Adult; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood*; D014280:Triglycerides / Q000097:blood*
chemical_list: C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D008076:Cholesterol, HDL; D036361:Peptide Hormones; D014280:Triglycerides