Bojan Polic
University of Rijeka School of Medicine, Rijeka, Croatia
Title: Immune sensing of the fat tissue in Obesity: The role of NK cells
Biography
Biography: Bojan Polic
Abstract
Obesity is an increasingly common health issue that predisposes people to metabolic disorders such as insulin resistance (IR), which can progress to diabetes mellitus type 2 (DM2). An important underlying cause of obesity-induced IR is chronic systemic inflammation derived from accumulating pro-inflammatory macro-phages in visceral adipose tissue (VAT). Currently, it is unknown which signal initiates adipose tissue macro phage (ATM) activation in VAT. We find that a phenotypically distinct VAT-resident NK cells provide a crucial link between obesity-induced adipose tissue stress and ATM activation in VAT. Ligands for the NK cell- activating receptor NKp46/Ncr1 are expressed in human and mouse VAT. Feeding with high-fat diet causes up regulation of Ncr1-ligands on adipocytes, leading to localized activation and cellular increase of NK cells. IFNγ produced by these cells drives early pro-inflammatory macro phage differentiation and promotes obesity-induced insulin resistance. Lack of NK cells, Ncr1 or IFNγ prevents macro phage activation in VAT and greatly ameliorates glucose tolerance and insulin sensitivity. Therapeutic blocking of Ncr1-signaling forestalls ATM activation. Our study identifies NK cells as key regulators of macrophage polarization and insulin resistance in response to obesity-induced adipose stress. The NK-ATM axis therefore provides an attractive new target for early treatment of patients with metabolic syndrome to prevent progression to DM2.