The Role of Nuclear Envelope Protein Lamin A in the Obesity-Induced Inflammation
  • Kae Won Cho
  • SLS Colloquia / 2018.03.08.(Thu) 04:00 pm / Room N104, Bldg 110

Obesity-induced chronic low-grade inflammation contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to examine whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from mice with obesity and obese individuals. Flow cytometry analysis further reveals that lamin A/C level was specifically increased in adipose tissue macrophages (ATMs). We also show that ectopic overexpression of lamin A/C in macrophages in vitro spontaneously increases the gene expression levels of Il6, Tnf, and Ccl2 with accompanied with activated NFkB translocation. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced upregulation of inflammatory genes. Importantly, we find that the myeloid cell specific Lmna deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates ATM proinflammatory changes in adipose tissue during obesity, and we propose lamin A/C as a potential therapeutic target for obesity-induced metabolic diseases.