The Role of Adipose-Derived Inflammatory Cytokines in Type 1 Diabetes —Adipose Tissue and T1D

Adipocyte dysfunction correlates with the development of diabetes. Recent studies suggest that adipose tissue is not simply the organ that stores fat and regulates lipid metabolism, but also is the largest endocrine organ with immune functions. Mice with an adipocyte-specific deletion of a SUMOspecific protease SENP1 develop symptoms of type-1 diabetes mellitus (T1DM) resulted from beta cell damage. Cytokine profiling indicates that peri-pancreatic adipocytes (PATs) of SENP1-dificient mice have increased proinflammatory cytokine production compared with other adipose depots. Proinflammatory cytokines originated from PATs have direct cytotoxic effects on pancreatic islets, and also increase infiltration of immune cells by augmenting CCL5 expression in adjacent pancreatic islets. Molecular analyses support that SUMOylation of NF-κB essential molecule (NEMO) in PATs leads to increased NF-κB activity, cytokine production and pancreatic inflammation. Therapeutic attempting to ameliorate the T1DM phenotype should consider using of NF-κB inhibitor against adipocyte inflammation.