Pentraxin 3 deficiency protects from the metabolic inflammation associated to diet-induced obesity.

Abstract

AIM\nLow-grade chronic inflammation characterizes obesity and metabolic syndrome. Here we aim at investigating the impact of the acute-phase protein long pentraxin 3 (PTX3) on the immune-inflammatory response occurring during diet-induced obesity.\n\n\nMETHODS AND RESULTS\nPTX3 deficiency in mice fed a high fat diet for 20 weeks protects from weight gain and adipose tissue deposition in visceral and subcutaneous depots. This effect is not related to changes in glucose homeostasis and lipid metabolism but is associated with the improved immune cell phenotype in the adipose tissue of Ptx3 deficient animals which is characterized by M2-macrophages polarization and increased angiogenesis. These findings are recapitulated in humans where carriers of a PTX3 haplotype (PTX3 h2/h2 haplotype), resulting in lower PTX3 plasma levels, presented with a reduced prevalence of obesity and decreased abdominal adiposity compared to non-carriers.\n\n\nCONCLUSIONS\nOur results support a critical role for PTX3 in the onset of obesity by promoting inflammation and limiting adipose tissue vascularization and delineate PTX3 targeting as a valuable strategy for the treatment of adipose tissue-associated inflammatory response.