Atherobesity - DFG KFO 152 "Fett und Gefäß"

Subproject 1:
Phase 1: Predictors and mechanism of endothelial dysfunction in obese children
Phase 2: Predictors and mechanism of early cardiovascular consequences resulting from children's obesity

Principal Investigators:

 

Dr. med. Antje Körner Dr. med. Sandra Erbs
Child and Adolescent Medicine Clinic Heart Center Leipzig GmbH
Universität Leipzig Universität Leipzig
Liebigstraße 21 Strümpellstraße 39
04103 Leipzig 04289 Leipzig
Phone: +49 341 97 26068 Phone: +49 341 8651428
Fax: +49 341 97 26009 Fax: +49 341 8651461
antje.koerner@medizin.uni-leipzig.de sandra.erbs@medizin.uni-leipzig.de

 

Summary of Subproject 1:

Phase 1:

The objective of this subproject is to define the connection between obesity and endothelial dysfunction as obligatory early stage of atherosclerosis in childhood.
The focus will be on the role of atherogenic factors of adipose tissue and the impact of the endothelium’s regenerative capacity in the pathogenesis of endothelial dysfunction. Initially the prevalence of endothelial dysfunction between obese children (n=90) and an age-matched normal control group (n=60) is compared in a cross-sectional study. The extent of endothelial dysfunction is correlated with classic atherogenic factors (dyslipidemia, adhesion molecules, lipoprotein (a), etc.) and with mediators from fatty tissue (adipocytocines). In the subsequent follow up, the detailed cardiovascular phenotyping including functional measurement of endothelial function will be repeated in two-year intervals and the incidence of arterial hypertension and pathological glucose tolerance will be registered. Additional mediators of oxidative stress and the regenerative capacity of the endothelium will be analyzed as pathogenetic factors influencing endothelial function by measurement of number and function of the circulating endothelial progenitor cells. Finally, we perform an intervention study to assess, whether a partial correction of endothelial dysfunction is possible through physical training of school children and whether sport can influence the atherogenic  risk profile favorably.

Phase 2:

The pathogenetic mechanisms leading to obesity related diseases are likely to be effective already at childhood age. Compared to lean children obese children showed increased blood pressure, endothelial dysfunction and a reduced number of endothelial progenitor cells (EPCs) as an early marker of developing vascular damage and an affected regenerative capacity of the endothelium.
The renewal project aims to characterize the direct relationship between the development of obesity and early stages of atherosclerosis in childhood and to analyze the interaction between atherogenic factors derived from adipose tissue and the regenerative capacity of endothelium. Therefore we will pursue the dynamic of blood-pressure profile, endothelial function and ECPs in relation to weight development and atherogenic risk profile loningitudinally in the established cohort. The direct role of adipose tissue will be evaluated with molecular and phenotypic changes of fatty tissue in the development of children's obesity. We will analyze pathogenetic factors like adipocytocines and their association with clinical parameters and the direct effects on the function of ECPs. Finally the positive effects of physical training on endothelial function and ECPs in lean and obese children will be evaluated.

Publications:

  1. Friebe D, Neef M, Kratzsch J, A., Erbs S, , Dittrich K, Garten A, Petzold-Quinque S, Blüher S, Reinehr T, Stumvoll M, Blüher M, Kiess W, Körner A. Leukocytes are a major source of circulating NAMPT/PBEF/visfatin linking obesity and inflammation in humans. Diabetologia. 2011;54:1200-11.
  2. Friebe D, Neef M, Erbs S, Dittrich K, Kratzsch J et al: RBP4 is primarily associated with adipose tissue mass in children. Int J Pediatr Obes. 2010;Epub ahead of print.
  3. Körner A, Neef M, Friebe D, Erbs S , Kratzsch J et al. Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children. Int J Obes (Lond). 2011;35:578-86.
  4. Walther C, Gaede L, Adams V, Gelbrich G, Leichtle A et al. Effect of increased exercise in school children on physical fitness and endothelial progenitor cells: a prospective randomized trial. Circulation. 2009;120:2251-2259.
  5. Meyre D, Delplanque J, Chevre JC, Lecoeur C, Lobbens S et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet. 2009;41:157-159.
  6. Benzinou M, Creemers JW, Choquet H, Lobbens S, Dina C et al. Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat Genet. 2008;40:943-945.
  7. Walther C, Adams V, Bothur I, Drechsler K, Fikenzer S et al. Increasing physical education in high school students: effects on concentration of circulating endothelial progenitor cells. Eur J Cardiovasc Prev Rehabil. 2008;15:416-422.
  8. Dina C, Meyre D, Gallina S, Durand E, Körner A et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007;39:724-726.
  9. Körner A , Garten A, Blüher M, Tauscher R, Kratzsch J et al. Molecular characteristics of serum visfatin and differential detection by immunoassays. J Clin Endocrinol Metab. 2007;92:4783-4791.
  10. Revollo JR, Körner A , Mills KF, Satoh A, Wang T et al. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 2007;6:363-375.
Imprint | Contact | © 2014 Author: Prof. Dr. M. Blüher