An explanation for recent discrepancies in levels of human circulating betatrophin
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To the Editor: In addition to hyperglycaemia and hyperinsulinaemia, type 2 diabetes mellitus is often associated with hypertriglyceridaemia. Recently, we and others have identified a novel circulating factor, referred to as lipasin , refeeding induced in fat and liver (RIFL) , angiopoietin-like protein 8 (ANGPTL8) [3, 4], and betatrophin , which may have a dual role in mediating both triacylglycerol metabolism and glucose homeostasis.
Lipasin mRNA levels in liver and fat, where it is predominantly expressed, are suppressed by fasting and highly induced by feeding and insulin resistance [1, 2, 3, 5]. Serum triacylglycerol levels are increased in lipasin overexpressing mice and decreased in lipasin knockout mice, and this likely occurs through a mechanism involving regulation of the activity of lipoprotein lipase (LPL) either directly  or indirectly by promoting ANGPTL3 cleavage . Indeed, the knockout mice exhibit higher LPL activity . The discovery of betatrophin as a...
KeywordsANGPTL8 Betatrophin C19orf80 Lipasin RIFL
Note added in proof
Consistent with the result of negative correlation between betatrophin and BMI based on the N-terminal kit (Fig. 1c), in a recent study, Gómez-Ambrosi et al  showed that circulating betatrophin is decreased in obesity.
This work was supported by a startup fund from Wayne State University to RZ.
Duality of interest
The authors confirm that there is no duality of interest associated with this manuscript.
ZF performed the experiments, analysed the data and participated in manuscript revision. ABA-S participated in data analysis and manuscript revision. RZ designed the study, analysed the data and wrote the manuscript. All authors have approved the final version. RZ is the guarantor of this work.
- 10.Chang JK, Lyu RM, Chen XQ et al (2013) Detection of C-terminal betatrophin peptides in human plasma and rodent liver. In: Nishiuchi Y, Teshima T (eds) The 4th Asia-Pacific International Peptide Symposium. Peptide Science, Japan, pp 243–246Google Scholar
- 11.Gómez-Ambrosi J, Pascual E, Catalán V et al (2014) Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes. J Clin Endocrinol Metab (in press)Google Scholar