ANGPTL8 (Betatrophin) is Expressed in Visceral Adipose Tissue and Relates to Human Hepatic Steatosis in Two Independent Clinical Collectives

Christian von Loeffelholz; Andreas F. H. Pfeiffer; Johan F. Lock; Steffi Lieske; Stephanie Döcke; Veronica Murahovschi; Jennifer Kriebel; Tonia de las Heras Gala; Harald Grallert; Natalia Rudovich; Martin Stockmann; Joachim Spranger; Gerhard Jahreis; Stefan R. Bornstein; George Lau; Aimin Xu; Jeanette Schulz-Menger; Louisa Exner; Sven Haufe; Jens Jordan; Stefan Engeli; Andreas L. Birkenfeld

doi:10.1055/s-0043-102950

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2017; 49(05): 343-349
DOI: 10.1055/s-0043-102950

Endocrine Care

ANGPTL8 (Betatrophin) is Expressed in Visceral Adipose Tissue and Relates to Human Hepatic Steatosis in Two Independent Clinical Collectives

Christian von Loeffelholz

¹Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

²Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany and Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany

³Department of Endocrinology, Diabetes, and Nutrition, Charité – Universitätsmedizin, Berlin, Germany

,

Andreas F. H. Pfeiffer

¹Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

³Department of Endocrinology, Diabetes, and Nutrition, Charité – Universitätsmedizin, Berlin, Germany

⁷German Center for Diabetes Research (DZD), Neuherberg, Germany

,

Johan F. Lock

⁴Department of General-, Visceral-, Vascular- and Paediatric Surgery, University Hospital of Wuerzburg, Wuerzburg, Germany

,

Steffi Lieske

⁵Section of Metabolic and Vascular Medicine, Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany

,

Stephanie Döcke

¹Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

,

Veronica Murahovschi

¹Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

,

Jennifer Kriebel

⁶Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany

⁷German Center for Diabetes Research (DZD), Neuherberg, Germany

⁸Institute of Epidemiology II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany

,

Tonia de las Heras Gala

⁹Research Unit of Diabetes Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

,

Harald Grallert

⁶Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany

⁷German Center for Diabetes Research (DZD), Neuherberg, Germany

⁸Institute of Epidemiology II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany

,

Natalia Rudovich

¹Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

³Department of Endocrinology, Diabetes, and Nutrition, Charité – Universitätsmedizin, Berlin, Germany

,

Martin Stockmann

¹⁰Department of General, Visceral and Transplantation Surgery, Charité – Universitätsmedizin, Berlin, Germany

,

Joachim Spranger

³Department of Endocrinology, Diabetes, and Nutrition, Charité – Universitätsmedizin, Berlin, Germany

,

Gerhard Jahreis

¹¹Institute of Nutrition, Friedrich Schiller University, Jena, Germany

,

Stefan R. Bornstein

⁵Section of Metabolic and Vascular Medicine, Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany

⁷German Center for Diabetes Research (DZD), Neuherberg, Germany

,

George Lau

¹²Humanity and Health GI and Liver Centre, University of Hong Kong, Hong Kong SAR, China

,

Aimin Xu

¹³Department of Pharmacology & Pharmacy, University of Hong Kong, Hong Kong SAR, China

,

Jeanette Schulz-Menger

¹⁴Department of Cardiology and Nephrology, Working Group on Cardiovascular Magnetic Resonance Imaging, Experimental and Clinical Research Center, Max-Delbrück-Centrum and Charité-Medical University Berlin and HELIOS Klinikum Berlin-Buch, Berlin, Germany

,

Louisa Exner

¹⁵Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

,

Sven Haufe

¹⁵Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

,

Jens Jordan

¹⁵Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

¹⁸Institute for Aerospace Medicine, German Aerospace Center, Cologne, Germany

,

Stefan Engeli^*

¹⁵Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

,

Andreas L. Birkenfeld^*

⁵Section of Metabolic and Vascular Medicine, Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany

⁷German Center for Diabetes Research (DZD), Neuherberg, Germany

¹⁶Competence Center for Metabolic Vascular Medicine Prof. Hanefeld, GWT- TU Dresden, Dresden, Germany

¹⁷Section of Diabetes and Nutritional Sciences, King’s College London, London, UK

› Institutsangaben

Abstract

Angiopoietin-like protein 8 (ANGPTL8)/betatrophin expression in visceral adipose tissue and associations with circulating fatty acid profile have not yet been investigated.

Forty subjects were included in a cross-sectional study, 57 in a dietary weight reduction intervention. Circulating Angiopoietin-like protein 8/betatrophin was measured in all subjects. Liver and adipose tissue were sampled and plasma fatty acids and tissue Angiopoietin-like protein 8/betatrophin expression were evaluated in the cross-sectional study. In the intervention study oral glucose testing and liver magnetic resonance scanning at baseline and after 6 months were performed. Angiopoietin-like protein 8/betatrophin mRNA was increased in visceral compared to subcutaneous adipose tissue (p<0.001). Circulating ANGPTL8/betatrophin correlated with liver steatosis (r=0.42, p=0.047), triacylglycerols (r=0.34, p=0.046), saturated (r=0.43, p=0.022), monounsaturated (r=0.51, p=0.007), and polyunsaturated fatty acids (r=−0.53, p=0.004). In the intervention study, baseline Angiopoietin-like protein 8/betatrophin correlated with age (r=0.32, p=0.010) and triacylglycerols (r=0.30, p=0.02) and was increased with hepatic steatosis (p=0.033). Weight loss reduced liver fat by 45% and circulating Angiopoietin-like protein 8/betatrophin by 11% (288±17 vs. 258±17 pg/ml; p=0.015). Angiopoietin-like protein 8/betatrophin is related to liver steatosis, while visceral adipose tissue represents an additional site of expression in humans.

Key words

diabetes - fatty acids - insulin resistance - fatty liver - hepatokine - HDL - LDL - triacylglycerides

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Referenzen

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