Wednesday, March 11, 2015

NK cell activation initiates type II diabetes

Type II diabetes is a complex syndrome involving endocrine, immune and metabolic abnormalities. It is well known that obesity can lead to type II diabetes. But how?

New study in Nature Immunology suggests that obesity-induced adipocyte stress activates NK cells  via NCR1 receptor driving IFN-γ mediated insulin insensitivity characteristic to type II diabetes.

The authors observed that NK cell depletion in mice fed high fat diet (HFD) ameliorated insulin insensitivity and glucose intolerance.


Ex vivo examination of visceral adipose tissue (VAT), a target tissue of type II diabetes, revealed that HFD induced expression of NK cell ligand in VAT detected by NCR1 (NKp46 in humans).


Interestingly, VAT but not subcutaneous (Sc fat) adipose tissue from HFD fed mice could stimulate NK cells.

In vivo experiments confirmed that NCR1 deficiency improved insulin sensitivity.


Finally, the authors showed that IFN-γ derived from NCR1 activated NK cells promotes inflammatory macrophages in VAT leading to glucose intolerance, that can be ameliorated with NCR1 blockade.


In summary, these results showed that HFD induces visceral adipose tissue stress that activates local NK cells via NCR1 ligand leading to inflammatory macrophage polarization and reduced insulin sensitivity. Targeting NK cell activation may interrupt this disease cycle and improve type II diabetes management.

I was always wondered why diet-induced obesity leading to VAT stress should activate inflammatory, M1 type macrophages? What is an evolutionary advantage for such response, in general? No idea.  

David Usharauli


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