Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals
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The newly identified liver- and fat-derived hormone, betatrophin, has recently been linked to insulin resistance and pancreatic beta cell growth in mice. These preclinical findings have suggested betatrophin as a potential candidate for novel glucose-lowering treatment concepts involving beta cell regeneration. However, the role of betatrophin in human insulin resistance and type 2 diabetes is currently unknown. Hence, the aim of this study was to investigate circulating betatrophin concentrations in two distinct cohorts with insulin resistance.
Betatrophin concentrations were analysed in (1) age- and sex-matched lean (n = 20) and morbidly obese individuals (n = 19), and (2) age-, sex- and BMI-matched non-diabetic (n = 19) and type 2 diabetic individuals (n = 18).
Betatrophin concentrations did not differ between lean and morbidly obese or between non-diabetic and type 2 diabetic participants. No association was found with variables of beta cell function and glucose homeostasis. However, betatrophin did correlate significantly with plasma atherogenic lipids including total cholesterol, LDL-cholesterol and apolipoprotein B in morbidly obese and type 2 diabetic patients but not in controls. Insulin-resistant individuals with hypercholesterolaemia (≥5.2 mmol/l) had significantly higher betatrophin concentrations than those with normal cholesterol (<5.2 mmol/l).
Betatrophin is a recently identified hormone, the circulating concentrations of which are unaltered in human insulin resistance but correlate significantly with atherogenic lipid profiles in high-risk cohorts with morbid obesity or type 2 diabetes. Betatrophin could therefore be a novel pathomechanistic player in dysfunctional lipid metabolism associated with high cardiovascular risk.
KeywordsANGPTL8 Betatrophin Insulin resistance Lipid metabolism LDL-cholesterol
We thank M. Zeyda (Medical University of Vienna) for expert opinion and professional advice.
This work was supported by the Vienna Science and Technology Fund (WWTF) through project LS12-059 (to FWK), the Federal Ministry of Economy, Family and Youth, and the National Foundation for Research, Technology and Development (to TMS), and the Austrian Research Promotion Agency through FEMtech FTI-project 821940 (to AK-W).
Duality of interest
The authors confirm that there is no duality of interest associated with this manuscript.
AF, BKI, LK, MF-S, AK-W, TMS and FWK contributed to study design, data acquisition, interpretation of data, and revision of the manuscript critically for important intellectual content and gave final approval of the version to be published. AF and FWK wrote the manuscript. FWK is the guarantor of this work.