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Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals

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Abstract

Aims/hypothesis

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.

Methods

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).

Results

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).

Conclusions/interpretation

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.

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Fig. 1

Abbreviations

ANGPTL:

Angiopoietin-like protein

HDL-C:

HDL-cholesterol

LDL-C:

LDL-cholesterol

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Acknowledgements

We thank M. Zeyda (Medical University of Vienna) for expert opinion and professional advice.

Funding

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.

Contribution statement

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.

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Authors and Affiliations

  1. Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Anna Fenzl, Bianca K. Itariu, Lana Kosi, Alexandra Kautzky-Willer, Thomas M. Stulnig & Florian W. Kiefer

  2. Christian Doppler-Laboratory for Cardio-Metabolic Immunotherapy, Medical University of Vienna, Vienna, Austria

    Bianca K. Itariu & Thomas M. Stulnig

  3. Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria

    Monika Fritzer-Szekeres

Authors
  1. Anna Fenzl
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  2. Bianca K. Itariu
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  3. Lana Kosi
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  4. Monika Fritzer-Szekeres
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  5. Alexandra Kautzky-Willer
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  6. Thomas M. Stulnig
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  7. Florian W. Kiefer
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Corresponding author

Correspondence to Florian W. Kiefer.

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Fenzl, A., Itariu, B.K., Kosi, L. et al. Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals. Diabetologia 57, 1204–1208 (2014). https://doi.org/10.1007/s00125-014-3208-x

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  • DOI: https://doi.org/10.1007/s00125-014-3208-x

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