Student or educator? Sign up with your school email and get 6 months of Pro free.
Cited by 241

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Identification and Validation of Novel Adipokines Released from Primary Human Adipocytes

Open access
Lehr, Stefan, Hartwig, Sonja, Lamers, Daniela, Famulla, Susanne, Müller, Stefan, Hanisch, Franz-Georg, Cuvelier, Claude, Ruige, Johannes, Eckardt, Kristin, Ouwens, D. Margriet, Sell, Henrike, Eckel, Juergen·2012·Molecular & Cellular Proteomics

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, αB-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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1074/mcp.m111.010504

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 4 references

Research works printed but not linked: 53

  1. Arner, 2003, The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones, Trends Endocrinol. Metab, 14, 137, 10.1016/S1043-2760(03)00024-9 · DOI · Paper page
  2. Scherer, 2006, Adipose tissue: from lipid storage compartment to endocrine organ, Diabetes, 55, 1537, 10.2337/db06-0263 · DOI · Paper page
  3. Kershaw, 2004, Adipose tissue as an endocrine organ, J. Clin. Endocrinol. Metab, 89, 2548, 10.1210/jc.2004-0395 · DOI · Paper page
  4. Waki, 2007, Endocrine functions of adipose tissue, Annu. Rev. Pathol, 2, 31, 10.1146/annurev.pathol.2.010506.091859 · DOI · Paper page
  5. Ouwens, 2010, The role of epicardial and perivascular adipose tissue in the pathophysiology of cardiovascular disease, J. Cell Mol. Med, 14, 2223, 10.1111/j.1582-4934.2010.01141.x · DOI · Paper page
  6. Breitling, 2009, Robust signaling networks of the adipose secretome, Trends Endocrinol. Metab, 20, 1, 10.1016/j.tem.2008.08.006 · DOI
  7. Sell, 2006, The adipocyte-myocyte axis in insulin resistance, Trends Endocrinol. Metab, 17, 416, 10.1016/j.tem.2006.10.010 · DOI
  8. Chen, 2005, Quantitative proteomic analysis of the secretory proteins from rat adipose cells using a 2D liquid chromatography-MS/MS approach, J. Proteome. Res, 4, 570, 10.1021/pr049772a · DOI
  9. Klimcakova, 2007, Profiling of adipokines secreted from human subcutaneous adipose tissue in response to PPAR agonists, Biochem. Biophys. Res. Commun, 358, 897, 10.1016/j.bbrc.2007.05.012 · DOI
  10. Kratchmarova, 2002, A proteomic approach for identification of secreted proteins during the differentiation of 3T3-L1 preadipocytes to adipocytes, Mol. Cell Proteomics, 1, 213, 10.1074/mcp.M200006-MCP200 · DOI · Paper page
  11. Tsuruga, 2000, Identification of novel membrane and secreted proteins upregulated during adipocyte differentiation, Biochem. Biophys. Res. Commun, 272, 293, 10.1006/bbrc.2000.2759 · doi:10.1006/bbrc.2000.2759
  12. Alvarez-Llamas, 2007, Characterization of the human visceral adipose tissue secretome, Mol. Cell Proteomics, 6, 589, 10.1074/mcp.M600265-MCP200 · DOI · Paper page
  13. Kim, 2010, Comparative analysis of the secretory proteome of human adipose stromal vascular fraction cells during adipogenesis, Proteomics, 10, 394, 10.1002/pmic.200900218 · DOI
  14. Rosenow, 2010, Identification of novel human adipocyte secreted proteins by using SGBS cells, J. Proteome. Res, 9, 5389, 10.1021/pr100621g · DOI
  15. Zhong, 2010, Temporal profiling of the secretome during adipogenesis in humans, J. Proteome. Res, 9, 5228, 10.1021/pr100521c · DOI
  16. Dietze-Schroeder, 2005, Autocrine action of adiponectin on human fat cells prevents the release of insulin resistance-inducing factors, Diabetes, 54, 2003, 10.2337/diabetes.54.7.2003 · DOI
  17. Lamers, 2011, Oleic acid and adipokines synergize in inducing proliferation and inflammatory signaling in human vascular smooth muscle cells, J. Cell Mol. Med, 15, 1177, 10.1111/j.1582-4934.2010.01099.x · DOI
  18. Sell, 2006, Monocyte chemotactic protein-1 is a potential player in the negative cross-talk between adipose tissue and skeletal muscle, Endocrinology, 147, 2458, 10.1210/en.2005-0969 · DOI · Paper page
  19. Thiele, 2010, Bioinformatics strategies in life sciences: From data processing and data warehousing to biological knowledge extraction, J. Integn. Bioinform, 7, 485
  20. Lehr, 2005, Effect of sterol regulatory element binding protein-1a on the mitochondrial protein pattern in human liver cells detected by 2D-DIGE, Biochemistry, 44, 5117, 10.1021/bi0479656 · doi:10.1021/bi0479656
  21. Rabilloud, 2001, A comparison between Sypro Ruby and ruthenium II tris (bathophenanthroline disulfonate) as fluorescent stains for protein detection in gels, Proteomics, 1, 699, 10.1002/1615-9861(200104)1:5<699::AID-PROT699>3.0.CO;2-C · DOI · Paper page
  22. Tchoukalova, 2003, A quick, reliable, and automated method for fat cell sizing, J. Lipid Res, 44, 1795, 10.1194/jlr.D300001-JLR200 · DOI
  23. Famulla, 2010, Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells, Int. J. Obes. (Lond.), 35, 762, 10.1038/ijo.2010.212 · DOI
  24. Lamers, 2011, Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome, Diabetes, 60, 1917, 10.2337/db10-1707 · DOI · Paper page
  25. Orci, 1991, Brefeldin A, a drug that blocks secretion, prevents the assembly of non-clathrin-coated buds on Golgi cisternae, Cell, 64, 1183, 10.1016/0092-8674(91)90273-2 · DOI · Paper page
  26. Wang, 2004, Profiling of the secreted proteins during 3T3-L1 adipocyte differentiation leads to the identification of novel adipokines, Cell Mol. Life Sci, 61, 2405, 10.1007/s00018-004-4256-z · DOI · Paper page
  27. Moreno-Navarrete, 2010, Complement factor H is expressed in adipose tissue in association with insulin resistance, Diabetes, 59, 200, 10.2337/db09-0700 · DOI
  28. Peake, 1997, Detection and quantification of the control proteins of the alternative pathway of complement in 3T3-L1 adipocytes, Eur. J. Clin. Invest, 27, 922, 10.1046/j.1365-2362.1997.2090759.x · DOI
  29. Kumar, 2005, Elevated expression of alphaA- and alphaB-crystallins in streptozotocin-induced diabetic rat, Arch. Biochem. Biophys, 444, 77, 10.1016/j.abb.2005.09.021 · DOI
  30. Tran, 2010, Transplantation of adipose tissue and stem cells: role in metabolism and disease, Nat. Rev. Endocrinol, 6, 195, 10.1038/nrendo.2010.20 · DOI · Paper page
  31. Wang, 2003, AlphaB-crystallin modulates protein aggregation of abnormal desmin, Circ. Res, 93, 998, 10.1161/01.RES.0000102401.77712.ED · DOI
  32. Vicart, 1998, A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy, Nat. Genet, 20, 92, 10.1038/1765 · DOI · Paper page
  33. Lorenzo, 1998, A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age, J. Biol. Chem, 273, 23463, 10.1074/jbc.273.36.23463 · DOI · Paper page
  34. Lorenzo, 1999, The human CILP gene: exon/intron organization and chromosomal mapping, Matrix Biol, 18, 445, 10.1016/S0945-053X(99)00035-9 · doi:10.1016/s0945-053x(99)00035-9
  35. Tsuruha, 2001, Implication of cartilage intermediate layer protein in cartilage destruction in subsets of patients with osteoarthritis and rheumatoid arthritis, Arthritis Rheum, 44, 838, 10.1002/1529-0131(200104)44:4<838::AID-ANR140>3.0.CO;2-C · doi:10.1002/1529-0131(200104)44:4<838::aid-anr140>3.0.co;2-c
  36. Johnson, 2001, Up-regulated expression of the phosphodiesterase nucleotide pyrophosphatase family member PC-1 is a marker and pathogenic factor for knee meniscal cartilage matrix calcification, Arthritis Rheum, 44, 1071, 10.1002/1529-0131(200105)44:5<1071::AID-ANR187>3.0.CO;2-3 · DOI · Paper page
  37. Lorenzo, 1998, Cloning and deduced amino acid sequence of a novel cartilage protein (CILP) identifies a proform including a nucleotide pyrophosphohydrolase, J. Biol. Chem, 273, 23469, 10.1074/jbc.273.36.23469 · DOI
  38. Masuda, 1997, Molecular cloning and expression of a porcine chondrocyte nucleotide pyrophosphohydrolase, Gene, 197, 277, 10.1016/S0378-1119(97)00272-2 · doi:10.1016/s0378-1119(97)00272-2
  39. Masuda, 2001, Variations in site and levels of expression of chondrocyte nucleotide pyrophosphohydrolase with aging, J. Bone Miner. Res, 16, 868, 10.1359/jbmr.2001.16.5.868 · doi:10.1359/jbmr.2001.16.5.868
  40. Mori, 2006, Transcriptional regulation of the cartilage intermediate layer protein (CILP) gene, Biochem. Biophys. Res. Commun, 341, 121, 10.1016/j.bbrc.2005.12.159 · doi:10.1016/j.bbrc.2005.12.159
  41. Seki, 2005, A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease, Nat. Genet, 37, 607, 10.1038/ng1557 · DOI · Paper page
  42. Locklin, 1999, Effects of TGFbeta and bFGF on the differentiation of human bone marrow stromal fibroblasts, Cell Biol. Int, 23, 185, 10.1006/cbir.1998.0338 · DOI
  43. Fain, 2005, Transforming growth factor beta1 release by human adipose tissue is enhanced in obesity, Metabolism, 54, 1546, 10.1016/j.metabol.2005.05.024 · DOI
  44. Mandal, 2010, Anti-inflammatory pathways and alcoholic liver disease: role of an adiponectin/interleukin-10/heme oxygenase-1 pathway, World J. Gastroenterol, 16, 1330, 10.3748/wjg.v16.i11.1330 · DOI
  45. Bao, 2010, Plasma heme oxygenase-1 concentration is elevated in individuals with type 2 diabetes mellitus, PLoS One, 5, e12371, 10.1371/journal.pone.0012371 · DOI
  46. Mateo, 2010, Serum heme oxygenase-1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease, Acta Neurol. Scand, 121, 136, 10.1111/j.1600-0404.2009.01261.x · DOI
  47. Miyazaki, 2010, Serum HO-1 is useful to make differential diagnosis of secondary hemophagocytic syndrome from other similar hematological conditions, Int. J. Hematol, 91, 229, 10.1007/s12185-010-0495-y · DOI
  48. Schipper, 2000, Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD, Neurology, 54, 1297, 10.1212/WNL.54.6.1297 · DOI
  49. Fernández, 2003, Expression of heme oxygenase-1 and regulation by cytokines in human osteoarthritic chondrocytes, Biochem. Pharmacol, 66, 2049, 10.1016/S0006-2952(03)00543-4 · DOI
  50. Kirino, 2007, Tumor necrosis factor alpha acceleration of inflammatory responses by down-regulating heme oxygenase 1 in human peripheral monocytes, Arthritis Rheum, 56, 464, 10.1002/art.22370 · DOI
  51. Kim, 2008, Heme oxygenase-mediated increases in adiponectin decrease fat content and inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 in Zucker rats and reduce adipogenesis in human mesenchymal stem cells, J. Pharmacol. Exp. Ther, 325, 833, 10.1124/jpet.107.135285 · DOI
  52. Li, 2008, Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance, Diabetes, 57, 1526, 10.2337/db07-1764 · DOI · Paper page
  53. Ryter, 2006, Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications, Physiol. Rev, 86, 583, 10.1152/physrev.00011.2005 · DOI · Paper page

Cited by

See all 241

Metadata

Authors
Lehr, S., Hartwig, S., Lamers, D., Famulla, S., Müller, S., Hanisch, F.-G., Cuvelier, C., Ruige, J., Eckardt, K., Ouwens, D. M., Sell, H., & Eckel, J.
Venue
Molecular & Cellular Proteomics
Publisher
Elsevier BV
Published
2012-01
Volume
11
Issue
1
Pages
M111.010504
ISSN
1535-9476 (ISSN-L)
OpenAlex
W2160610888
Cited by
241
References
4
FWCI
13.40
Type
journal article
Language
en
Open access
hybrid
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Identification and Validation of Novel Adipokines Released from Primary Human Adipocytes. https://app.cochat.ai/papers/10.1074/mcp.m111.010504
The paper
Lehr, S., Hartwig, S., Lamers, D., Famulla, S., Müller, S., Hanisch, F.-G., Cuvelier, C., Ruige, J., Eckardt, K., Ouwens, D. M., Sell, H., & Eckel, J. (2012). Identification and Validation of Novel Adipokines Released from Primary Human Adipocytes. Molecular & Cellular Proteomics. https://doi.org/10.1074/mcp.m111.010504

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.