Horm Metab Res 2009; 41(3): 190-196
DOI: 10.1055/s-0028-1093342
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Effect of Conditioned Media from Mature Human Adipocytes on Insulin-stimulated Akt/PKB Phosphorylation in Human Skeletal Muscle Cells: Role of BMI and Fat Cell Size

T. Skurk 1 , C. Alberti-Huber 1 , H. Hauner 1
  • 1Else Kröner-Fresenius-Center for Nutritional Medicine, Life Science Center Weihenstephan, Technische Universität München, Munich, Germany
Further Information

Publication History

received 06.05.2008

accepted 28.08.2008

Publication Date:
27 October 2008 (online)

Abstract

Obesity is associated with chronic low-grade inflammation. It is currently hypothesized that products secreted from fat cells not only cause this proinflammatory condition but may also have a direct impact on the development of insulin resistance in skeletal muscle. The aim of this study was to investigate if adipocyte-conditioned media interfere with insulin-stimulated Akt/PKB phosphorylation in in vitro differentiated human skeletal muscle cells. Primary human skeletal muscle cells were exposed to adipocyte-conditioned media from subjects with a wide range of BMI. Insulin-induced phosphorylation of the signaling proteins Akt/PKB and ERK-2 was analyzed using a bead-based fluorescence detection system and was correlated to BMI and fat cell size. Adipocyte-conditioned media reduced insulin-stimulated Akt/PKB phosphorylation in a manner depending on BMI and fat cell volume. This inhibition in serine phosphorylation was comparable to that observed in TNF-α-treated control cultures. Conditioned media from omental adipocytes reduced Akt/PKB phosphorylation moderately to a greater extent compared to media from subcutaneous fat cells from the same donors (p<0.05). Furthermore, there were significant associations between the concentration of selected adipokines and Akt/PKB phosphorylation. These data provide first direct evidence that secreted factors from freshly isolated mature fat cells separated according fat cell size reduce insulin-stimulated Akt/PKB phosphorylation in human skeletal muscle cells and may contribute to the pathogenesis of obesity-associated insulin resistance.

References

Correspondence

T. Skurk, MD 

Else Kröner-Fresenius-Centre for Nutritional Medicine

Technische Universität München

Am Forum 5

85350 Freising-Weihenstephan

Germany

Phone: +49/8161/71 20 01

Fax: +49/8161/71 20 97

Email: [email protected]