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The caveolae‐associated coiled‐coil protein, NECC 2, regulates insulin signalling in Adipocytes
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The caveolae‐associated coiled‐coil protein, NECC 2, regulates insulin signalling in Adipocytes
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Journal Article
The caveolae‐associated coiled‐coil protein, NECC 2, regulates insulin signalling in Adipocytes
2018
Overview
Adipocyte dysfunction in obesity is commonly associated with impaired insulin signalling in adipocytes and insulin resistance. Insulin signalling has been associated with caveolae, which are coated by large complexes of caveolin and cavin proteins, along with proteins with membrane‐binding and remodelling properties. Here, we analysed the regulation and function of a component of caveolae involved in growth factor signalling in neuroendocrine cells, neuroendocrine long coiled‐coil protein‐2 (
NECC
2), in adipocytes. Studies in 3T3‐L1 cells showed that
NECC
2 expression increased during adipogenesis. Furthermore,
NECC
2 co‐immunoprecipitated with caveolin‐1 (
CAV
1) and exhibited a distribution pattern similar to that of the components of adipocyte caveolae,
CAV
1, Cavin1, the insulin receptor and cortical actin. Interestingly,
NECC
2 overexpression enhanced insulin‐activated Akt phosphorylation, whereas
NECC
2 downregulation impaired insulin‐induced phosphorylation of Akt and
ERK
2. Finally, an up‐regulation of
NECC
2
in subcutaneous and omental adipose tissue was found in association with human obesity and insulin resistance. This effect was also observed in 3T3‐L1 adipocytes exposed to hyperglycaemia/hyperinsulinemia. Overall, the present study identifies
NECC
2 as a component of adipocyte caveolae that is regulated in response to obesity and associated metabolic complications, and supports the contribution of this protein as a molecular scaffold modulating insulin signal transduction at these membrane microdomains.
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