Altered Concentrations in Dyslipidemia Evidence a Role for ANGPTL8/Betatrophin in Lipid Metabolism in Humans

• Published in: The journal of clinical endocrinology and metabolism 2016-10, Vol.101 (10), p.3803-3811
• Main Authors: Gómez-Ambrosi, Javier, Pascual-Corrales, Eider, Catalán, Victoria, Rodríguez, Amaia, Ramírez, Beatriz, Romero, Sonia, Vila, Neus, Ibáñez, Patricia, Margall, María A, Silva, Camilo, Gil, María J, Salvador, Javier, Frühbeck, Gema
• Format: Article
• Language: English
• Subjects: Adult; Angiopoietin-like Proteins; Cholesterol, HDL - blood; Diabetes Mellitus, Type 2 - blood; Dyslipidemias - blood; Female; Humans; Lipid Metabolism; Male; Middle Aged; Peptide Hormones - blood; Triglycerides - blood
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2016-2084

Context: 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. Objective: 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. Design, Setting, and Participants: 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. Results: 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. Conclusions: 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. Serum concentrations of ANGPTL8/betatrophin were measured in 93 patients with dyslipidemia and 84 control subjects. Circulating levels were significantly lower in individuals with dyslipidemia.