Functional annotation of the human fat cell secretome

Dahlman, Ingrid; Elsen, Manuela; Tennagels, Norbert; Korn, Marcus; Brockmann, B.; Sell, Henrike; Eckel, Jürgen; Arner, Peter

doi:10.3109/13813455.2012.685745

Cited by 95 publications

(68 citation statements)

References 24 publications

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“…It has also been shown to inhibit the pro-fibrotic connective tissue growth factor (Sabbah et al, 2011). Furthermore, WISP2 was recently identified as one of the top candidate secreted proteins in the development of obesity, as determined by fat depot DE between obese and lean humans (Dahlman et al, 2012).…”

Section: Marbling Physiology and Developmentmentioning

confidence: 99%

Longitudinal muscle gene expression patterns associated with differential intramuscular fat in cattle

Hudson

Reverter

Greenwood

et al. 2015

Animal

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Intramuscular fat (IMF) can improve meat product quality through its impact on flavour and juiciness. High marbling cuts can command premium prices in some countries and grading systems, but there is substantial cost involved in choosing to grain feed animals in an effort to deposit more IMF. There would be value in developing methods to predict predisposition to 'marble' well. Unfortunately, the biological mechanisms underpinning marbling remain a mystery: the key adipocyte cell populations have not been defined, there are no reliable DNA markers, no known (if any) causal mutations and gene expression analyses in the main have tended to characterise increases in expression of end-point fat metabolism proteins such as the fatty acid-binding proteins. To shed light on expression-based markers of marbling potential, we contrasted LD gene expression in high IMF Wagyu cross animals with a low IMF Piedmontese cross at various time points. The expected divergence in the fat metabolism genes FABP4, THRSP, CIDEC and ACACA between the breeds occurs surprisingly late in postnatal development at about 20 months. On the other hand, divergent expression of WISP2, RAI14 and CYP4F2 was discovered in animals at or before 12 months of age, suggesting these genes may have potential as earlier predictors of marbling potential. In line with other researchers, we found intriguing links between IMF development and connective tissue remodelling. WISP2 -a novel adipokine highly expressed and secreted by adipose precursor cells and an inhibitor of the pro-fibrotic connective tissue growth factor -emerges as a particularly attractive candidate. It is relatively upregulated in high marbling Wagyu before admission to feedlotting, somewhere between 7 and 12 months. This difference is subsequently maintained until 25 months, but not thereafter. RAI14, thought to play a role in porcine adipocyte differentiation and with links to retinoic acid metabolism, has an unusual expression profile. Its expression level increases monotonically with postnatal development, and is always higher in Wagyu than Piedmontese. Strong, sustained upregulation of the anti-inflammatory CYP4F2 in Piedmontese is consistent with Wagyu adiposity being a pro-inflammatory state. Application of regulatory impact factor analysis, a network method for identifying causal effector molecules, suggests marbling roles for transcription factors previously implicated in (1) the formation of liposarcoma (unconstrained fatty masses) (YEATS4, MDM2), (2) adipogenesis (CREBL2, SP1, STAT1) and (3) inflammation (ISGF3G, HOXB13, PML).

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Section: Marbling Physiology and Developmentmentioning

confidence: 99%

Longitudinal muscle gene expression patterns associated with differential intramuscular fat in cattle

Hudson

Reverter

Greenwood

et al. 2015

Animal

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“…We also found WISP2 to be a secreted protein, highly expressed in mesenchymal stem cells, fibroblasts, and preadipocytes and adipogenic differentiation was associated with a marked reduction in Wisp2 expression, whereas differentiation was inhibited by extracellular WISP2. WISP2 was also recently identified in a proteomics analysis of the secretome of human adipose tissue (14) and can thus be considered a novel secreted adipokine. However, the overall regulation of Wisp2 expression is unclear although canonical WNT ligands can increase it (12,13).…”

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confidence: 99%

The Novel Secreted Adipokine WNT1-inducible Signaling Pathway Protein 2 (WISP2) Is a Mesenchymal Cell Activator of Canonical WNT

Grünberg

Hammarstedt

Hedjazifar

et al. 2014

Journal of Biological Chemistry

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“…À cet égard, l'étude des BBS, qui a permis de révéler un rôle direct du tissu adipeux, complémentaire de celui de l'axe hypothalamique, est sans doute emblématique des futures recherches à mettre en oeuvre pour l'exploration de voies potentiellement associées au développement de l'obésité, et aussi pour l'identification de nouveaux biomarqueurs. L'obésité, maladie complexe et multifactorielle, a déjà été abordée via de nombreuses approches haut débit allant des études d'associations de type GWAS (genome wide association study) [52], des recherches de variants structuraux de type CNV (copy number variation) [53] ou des études de variations épigénétiques [54], jusqu'aux analyses basées sur des transcriptomes [55], protéomes [56], métabolomes [57] et récemment, des liposomes [58] ou des sécrétomes [59]. Cependant, au vu de nos résultats sur la biologie du tissu adipeux, ou des récents travaux sur la communication pancréas-tissu adipeux [60], seule une approche multi-niveaux, intégrant les différentes techniques haut débit pourra déchiffrer la variété des signaux et des communications interorganes (cross-talks) intervenant dans l'obésité ( Figure 1C).…”

Section: Perspectives Et Défis D'une Approche Intégrative Pour L'étudunclassified

Syndrome de Bardet-Biedl : cils et obésité

et al. 2014

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Functional annotation of the human fat cell secretome

Cited by 95 publications

References 24 publications

Longitudinal muscle gene expression patterns associated with differential intramuscular fat in cattle

Longitudinal muscle gene expression patterns associated with differential intramuscular fat in cattle

The Novel Secreted Adipokine WNT1-inducible Signaling Pathway Protein 2 (WISP2) Is a Mesenchymal Cell Activator of Canonical WNT

Syndrome de Bardet-Biedl : cils et obésité

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