Atherobesity - DFG KFO 152 "Fett und Gefäß"

Subproject 3: Heterogeneity of Adipose Tissue Molecular Mechanism of Visceral Fat Accumulation

Principal Investigator:

 

Prof. Dr. med. Matthias Blüher  
Endocrinology and Nephrology Clinic  
Universität Leipzig  
Liebigstraße 20  
04103 Leipzig  
Phone: +49 341 97 13829  
Fax: +49 341 97 13389  
matthias.blueher@medizin.uni-leipzig.de  

 

Summary of the Subproject:

In the first funding period, we identified new candidate genes and mechanisms in the development of visceral obesity. Immune cell infiltration , adipokine secretion, expression of developmental genes and the dynamics of adipogenesis and fat cell apoptosis seem to be important mechanisms which are differently regulated in the visceral and subcutaneous adipose tissue depots. We were able to identify progranulin as a new adipocyte-secreted chemoatractant factor for macrophages predominantly into visceral adipose tissue. Furthermore we were able to show that circulating proteins of the bone morphogenetic proteins (BMP) family and their receptors BMPR1 and 2 are involved in the development of obesity at an early stage.
The role of progranulin, BMP 2, 4 and 7 in the regulation of substantial properties of adipocytes shall initially be investigated in vitro. In addition to the characterization of these new candidates of visceral obesity in established human study groups, we will perform transplantation experiments with adipose tissue, preadipocytes and bone marrow cells of GFP-labelled mice to investigate the impact of progranulin and BMP 2, 4 and 7 on immune cell infiltration into adipose tissue and the differential dynamics of the recruitment and life cycle of fat cells.

Publications:

  1. Tönjes A, Fasshauer M, Kratzsch J, Stumvoll M, Blüher M. Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes. PLoS One. 2010;5:e13911.
  2. Klöting N, Berthold S, Kovacs P, Schön MR, Fasshauer M, Ruschke K, Stumvoll M, Blüher M. MicroRNA expression in human omental and subcutaneous adipose tissue. PLoS One. 2009;4:e4699.
  3. Youn BS, Bang SI, Klöting N, Park JW, Lee N, Oh JE, Pi KB, Lee TH, Ruschke K, Fasshauer M, Stumvoll M, Blüher M. Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes. 2009;58:627-36.
  4. Kralisch S, Stepan H, Kratzsch J, Verlohren M, Verlohren HJ, Drynda K, Lössner U, Blüher M, Stumvoll M, Fasshauer M. Serum levels of adipocyte fatty acid binding protein are increased in gestational diabetes mellitus. Eur J Endocrinol. 2009;160:33-8.
  5. Stein S, Bachmann A, Lössner U, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine FGF21 depend on renal function. Diabetes Care. 2009;32:126-8.
  6. Weise S, Kralisch S, Sommer G, Lossner U, Blüher M, Stumvoll M, Fasshauer M. Tissue inhibitor of metalloproteinase-1 mRNA production and protein secretion are induced by interleukin-1 beta in 3T3-L1 adipocytes. J Endocrinol. 2008;198:169-74.
  7. Fasshauer M, Waldeyer T, Seeger J, Schrey S, Ebert T, Kratzsch J, Lössner U, Blüher M, Stumvoll M, Faber R, Stepan H. Circulating high-molecular-weight adiponectin is upregulated in preeclampsia and is related to insulin sensitivity and renal function. Eur J Endocrinol. 2008;158:197-201.
  8. Seeger J, Ziegelmeier M, Bachmann A, Lössner U, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine vaspin in relation to metabolic and renal parameters. J Clin Endocrinol Metab. 2008;93:247-51.
  9. Blüher M, Williams CJ, Klöting N, Hsi A, Ruschke K, Oberbach A, Fasshauer M, Berndt J, Schön MR, Wolk A, Stumvoll M, Mantzoros CS. Gene expression of adiponectin receptors in human visceral and subcutaneous adipose tissue is related to insulin resistance and metabolic parameters and is altered in response to physical training. Diabetes Care. 2007;30:3110-5.
  10. Blüher M, Brennan AM, Kelesidis T, Kratzsch J, Fasshauer M, Kralisch S, Williams CJ, Mantzoros CS. Total and high-molecular weight adiponectin in relation to metabolic variables at baseline and in response to an exercise treatment program: comparative evaluation of three assays. Diabetes Care. 2007;30:280-5.
  11. Blüher M, Engeli S, Klöting N, Berndt J, Fasshauer M, Bátkai S, Pacher P, Schön MR, Jordan J, Stumvoll M. Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes. 2006;55:3053-60.
  12. Oberbach A, Tönjes A, Klöting N, Fasshauer M, Kratzsch J, Busse MW, Paschke R, Stumvoll M, Blüher M. Effect of a 4 week physical training program on plasma concentrations of inflammatory markers in patients with abnormal glucose tolerance. Eur J Endocrinol. 2006;154:577-85.
  13. Blüher M, Bullen JW Jr, Lee JH, Kralisch S, Fasshauer M, Klöting N, Niebauer J, Schön MR, Williams CJ, Mantzoros CS. Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training. J Clin Endocrinol Metab. 2006;91:2310-6
Imprint | Contact | ©2014 Author: Prof. Dr. M. Blüher