Altered Concentrations in Dyslipidemia Evidence a Role for ANGPTL8/Betatrophin in Lipid Metabolism in Humans
Gómez-Ambrosi J (1), Pascual-Corrales E (1), Catalán V (1), Rodríguez A (1), Ramírez B (1), Romero S (1), Vila N (1), Ibáñez P (1), Margall MA (1), Silva C (1), Gil MJ (1), Salvador J (1), Frühbeck G (1).
(1) 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, 31008 Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) (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, 31008 Pamplona, Spain; and Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA) (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.), 31008 Pamplona, Spain
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 HDL-cholesterol or triglycerides, respectively.
DESIGN, SETTING, AND PARTICIPANTS:
Serum concentrations of ANGPTL8/betatrophin were measured by 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<0.001 in both males (C 27.8 ± 15.2 vs DL 17.0 ± 11.2 ng/mL) and females (C 50.0 ± 22.2 vs DL 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 TG concentrations. ANGPTL8/betatrophin levels were lower in subjects with T2D (P<0.001) but the impact of T2D vanished (P=0.257) 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-C and a potential therapeutic tool for the treatment of dyslipidemia.
CITATION J Clin Endocrinol Metab. 2016 Jul 29:jc20162084