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

Abstract

Aims Low-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. Methods and results PTX3 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 an 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 with non-carriers. Conclusion Our 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.

Perspectives on long pentraxin 3 and rheumatoid arthritis: several potential breakthrough points relying on study foundation of the past

“…Obesity is usually the result of an imbalance of excess nutrients and metabolic homeostasis, leading to a chronic inflammatory state and an increase in systemic proinflammatory mediators and adipose tissue-retaining immune cells phenotype from tolerant to pro-inflamed. Once the immune cells in adipose tissue transform into proinflammatory phenotype, they will produce adipokines and inflammatory cytokines [39]. These factors promote the recruitment of immune cells, allowing the persistence of local and systemic inflammation.…”

Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health

“…Other edges specifically observed in the WIN positioned measures of activities and sleep in the proximity of several metabolites and proteins. Among the proteins, we observed well-known members of lipid metabolism pathways (LEP, LPL) and proteins with related functions (PTX3 31,32 , NRP1 33 , PRSS8 34 ). Correspondingly, FFA and FAEs appeared in this subnetwork.…”

Follow-up Evaluation of Association between Weight Changes, Metabolic, and Hormonal Outcomes in Children – a Single-center Pilot Study

“…Apart from classic markers, α-tumour necrosis factor, interleukin-6, and C-reactive protein, novel proteins are studied for indicating the inflammatory status in obese patients. 54,55 A strength of our study is that it is the first analysis of the metabolic and clinical changes as present in obesity-related comorbidities guideline in a Romanian center. In the Romanian pediatric population, cross-sectional epidemiological studies, as part of international projects such as JANPA (Joint Action on Nutrition and Physical Activity) 56 and COSI 2017 8 focused on prevalence and risk factors in obese children have been conducted.…”