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Identification and validation of novel adipokines released from primary human adipocytes

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Abstract
Adipose tissue is a major endocrine organ, releasing signaling and mediator proteins, termed adipokines, via which adipose tissue communicates with other organs. Expansion of adipose tissue in obesity alters adipokine secretion, which may contribute to the development of metabolic diseases. Although recent profiling studies have identified numerous adipokines, the amount of overlap from these studies indicates that the adipokinome is still incompletely characterized. Therefore, we conducted a complementary protein profiling on concentrated conditioned medium derived from primary human adipocytes. SDS-PAGE/liquid chromatography-electrospray ionization tandem MS and two-dimensional SDS-PAGE/matrix-assisted laser desorption ionization/time of flight MS identified 347 proteins, 263 of which were predicted to be secreted. Fourty-four proteins were identified as novel adipokines. Furthermore, we validated the regulation and release of selected adipokines in primary human adipocytes and in serum and adipose tissue biopsies from morbidly obese patients and normal-weight controls. Validation experiments conducted for complement factor H, alpha B-crystallin, cartilage intermediate-layer protein, and heme oxygenase-1 show that the release and expression of these factors in adipocytes is regulated by differentiation and stimuli, which affect insulin sensitivity, as well as by obesity. Heme oxygenase-1 especially reveals to be a novel adipokine of interest. In vivo, circulating levels and adipose tissue expression of heme oxygenase-1 are significantly increased in obese subjects compared with lean controls. Collectively, our profiling study of the human adipokinome expands the list of adipokines and further highlights the pivotal role of adipokines in the regulation of multiple biological processes within adipose tissue and their potential dysregulation in obesity.
Keywords
ALPHA-B-CRYSTALLIN, INTERMEDIATE LAYER PROTEIN, CHONDROCYTE NUCLEOTIDE PYROPHOSPHOHYDROLASE, NECROSIS-FACTOR-ALPHA, ADIPOSE-TISSUE, SECRETED PROTEINS, HEME OXYGENASE-1, INSULIN-RESISTANCE, ENDOCRINE ORGAN, STEM-CELLS

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Chicago
Lehr, Stefan, Sonja Hartwig, Daniela Lamers, Susanne Famulla, Stefan Müller, Franz-Georg Hanisch, Claude Cuvelier, et al. 2012. “Identification and Validation of Novel Adipokines Released from Primary Human Adipocytes.” Molecular & Cellular Proteomics 11 (1).
APA
Lehr, S., Hartwig, S., Lamers, D., Famulla, S., Müller, S., Hanisch, F.-G., Cuvelier, C., et al. (2012). Identification and validation of novel adipokines released from primary human adipocytes. MOLECULAR & CELLULAR PROTEOMICS, 11(1).
Vancouver
1.
Lehr S, Hartwig S, Lamers D, Famulla S, Müller S, Hanisch F-G, et al. Identification and validation of novel adipokines released from primary human adipocytes. MOLECULAR & CELLULAR PROTEOMICS. 2012;11(1).
MLA
Lehr, Stefan, Sonja Hartwig, Daniela Lamers, et al. “Identification and Validation of Novel Adipokines Released from Primary Human Adipocytes.” MOLECULAR & CELLULAR PROTEOMICS 11.1 (2012): n. pag. Print.
@article{3092705,
  abstract     = {Adipose tissue is a major endocrine organ, releasing signaling and mediator proteins, termed adipokines, via which adipose tissue communicates with other organs. Expansion of adipose tissue in obesity alters adipokine secretion, which may contribute to the development of metabolic diseases. Although recent profiling studies have identified numerous adipokines, the amount of overlap from these studies indicates that the adipokinome is still incompletely characterized. Therefore, we conducted a complementary protein profiling on concentrated conditioned medium derived from primary human adipocytes. SDS-PAGE/liquid chromatography-electrospray ionization tandem MS and two-dimensional SDS-PAGE/matrix-assisted laser desorption ionization/time of flight MS identified 347 proteins, 263 of which were predicted to be secreted. Fourty-four proteins were identified as novel adipokines. Furthermore, we validated the regulation and release of selected adipokines in primary human adipocytes and in serum and adipose tissue biopsies from morbidly obese patients and normal-weight controls. Validation experiments conducted for complement factor H, alpha B-crystallin, cartilage intermediate-layer protein, and heme oxygenase-1 show that the release and expression of these factors in adipocytes is regulated by differentiation and stimuli, which affect insulin sensitivity, as well as by obesity. Heme oxygenase-1 especially reveals to be a novel adipokine of interest. In vivo, circulating levels and adipose tissue expression of heme oxygenase-1 are significantly increased in obese subjects compared with lean controls. Collectively, our profiling study of the human adipokinome expands the list of adipokines and further highlights the pivotal role of adipokines in the regulation of multiple biological processes within adipose tissue and their potential dysregulation in obesity.},
  author       = {Lehr, Stefan and Hartwig, Sonja and Lamers, Daniela and Famulla, Susanne and M{\"u}ller, Stefan and Hanisch, Franz-Georg and Cuvelier, Claude and Ruige, Johannes and Eckardt, Kristin and Ouwens, D Margriet and Sell, Henrike and Eckel, Juergen},
  issn         = {1535-9476},
  journal      = {MOLECULAR \& CELLULAR PROTEOMICS},
  language     = {eng},
  number       = {1},
  pages        = {13},
  title        = {Identification and validation of novel adipokines released from primary human adipocytes},
  url          = {http://dx.doi.org/10.1074/mcp.M111.010504},
  volume       = {11},
  year         = {2012},
}

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