SFEBES2015 Featured Posters (1) (12 abstracts)
Regulation of adipogenesis by wnt10b signalling in cultured human adipocytes taken from an obese patient with a WNT10B-C256Y mutation
Sahar Azharian 1 , Philip D Voyias 1 , Alice Murphy 1 , Lucia Martinez de la Escalera Clapp 1 , Antonysunil Adaikalakoteswari 1 , Ponnusamy Saravanan 1 , Milan K Piya 1, , Philip G McTernan 1 & Gyanendra Tripathi 1
1University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK; 2Institute of Digital Healthcare, University of Warwick, Coventry, UK.
Background: Adipogenesis is a key process leading to adipose tissue (AT) expansion. However, managing this event is critical to limit excessive fat accumulation and disease risk. Adipogenesis appears controlled in part, through Wnt10b signalling which reduces adipogenesis via inhibiting CCAAT/enhancer-binding protein alpha (CEBPα) although the molecular mechanism remains unclear.
Aims: Abdominal subcutaneous AT (AbdSc AT) was collected from a, non-diabetic metabolically normal obese, female subject with a naturally occurring WNT10B-C256Y mutation, (rendering a non-functional Wnt10b protein (Age: 19yr, BMI: 62Kg/m2)), to examine the impact of this mutation in Wnt10b signalling during in vitro adipogenesis.
Methods: AbdSc adipocytes were cultured from a WNT10B-C256Y subject and compared with control adipocyte cells from lean non-diabetic subjects (Age: 30.7 mean±S.E.M. 4.7 years, BMI: 21.9±1.2 kg/m2; n=3). Adipogenesis was assessed over time (0–14 days) by genes regulating adipogenesis and Wnt signalling as well as lipid accumulation, glycerol release and insulin-stimulated glucose uptake.
Results: During adipogenesis the WNT10B-C256Y cells accumulated significantly more lipid and insulin stimulated glucose uptake than control cells (P<0.05), whilst glycerol release remained similar. In WNT10B-C256Y adipocytes, mRNA CEBPα expression increased throughout adipogenesis still rising at Day 14, whereas in control cells this peaked at day 6. Whilst axis inhibition protein 2 (AXIN2, a key gene in regulating CEBPα) appeared down-regulated in the WNT10B-C256Y adipocytes in contrast to the control cells (P<0.01). WNT10B-C256Y adipocytes significantly raised phospho-β-catenin protein (P<0.05) and lowered T cell transcription factor 7 (TCF7) expression (P<0.05).
Conclusions: These data highlight that Wnt10b plays an inhibitory role in adipogenesis via a negative feedback loop to reduce CEBPα through AXIN2. Taken together this data indicates that the feedback loop is dysregulated in the subject with the WNT10B-C256Y mutation fuelling her continual fat accumulation, and future risk of metabolic disease.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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