Life Science

How fat cells become fat: Insights from phosphoproteomics

Adipocytes, or fat cells,  are  important  endocrine  and  metabolic  cells  critical  for  systemic  insulin sensitivity and both adipose excess and insufficiency are associated with adverse metabolic function. Mature adipocytes develop in a process called adipogenesis , whereby preadipocyte precursors differentiate into lipid laden fat cells. Adipogenesis  is  driven  by  a  network  of  transcriptional  regulators active at different stages of cell differentiation.


Rabiee, Jensen and colleagues  hypothesized that upon induction of adipogenesis, protein post-translational modifications (PTMs), in particular phosphorylation, play  a major  role  in  activating  and  propagating  signals  within the transcriptional regulators networks.  They applied mass spectrometry-based  quantitative proteomics and phosphoproteomics to monitor nuclear proteins during the first 4 hours of preadipocyte differentiation which revealed significant changes in the phosphorylation of multiple transcriptional regulators. Adipogenic stimuli increased the nuclear abundance and/or phosphorylation levels of proteins involved in gene expression, cell organization and oxidation-reduction  pathways, whereas  negative  modulators  of  gene  expression,  insulin  stimulated  glucose  uptake,  and  cytoskeletal organization showed the opposite trend. The researchers created a useful kinase-substrate database based on  the  relationship  between  protein  kinases  and  the identified protein  phosphorylation  sites and their results suggest that the cyclin-dependent kinase family and the mitogen activated protein kinase (MAPK) family act as orchestrators of early adipogenesis.

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