The long pentraxin 3 plays a key role in the immunomodulation of diet-induced obesity AIM: Obesity is characterized by a state of chronic low-grade inflammation. PTX3 is the prototype of long pentraxins, it is an essential component of the humoral arm of innate immunity and is involved in many inflammatory processes. There are several conflicting data about the role of PTX3 in obesity. Aim of this project was to clarify whether PTX3 behaves as a bystander or actively participates to obesity-related inflammation. METHODS: PTX3 KO and WT littermates were fed a high fat diet (HFD; 45% Kcal from fat) or a standard fata diet (SFD;10% Kcal from fat) for 20 weeks. Body weight was measured weekly; fat distribution (magnetic resonance for imaging, MRI) and glycemia (glucose-GTT and insulin-ITT tolerance tests) was checked at 10 and 20 weeks. Immunophenotyping and gene expression, in particular of the adipose tissue, was performed at 20 weeks. Ectopic fat deposition in h1/h1 and h2/h2 individuals was determined by DEXA. RESULTS: PTX3 KO mice on HFD exhibit a decreased weight gain compared to WT (AUC weight gain WT=190.8±17.45, KO=134.8±10.09), coupled to a decreased accumulation of visceral (VAT) and subcutaneous (SCAT) fat both at 10 (p<0.05) and 20 weeks (p<0.01) of diet measured by MRI and confirmed weighing the tissues after the sacrifice (VAT% WT=7.609±0.6776, KO=4.390±0.8235; SCAT% WT=5.953±0.9682, KO=3.144±0.6129, p<0.05). Basal glycemia and the results of the glucose and insulin tolerance test were superimposable. PTX3 deficiency results in the reduction of monocytes markers and pro-inflammatory cytokines gene expression in VAT (MCP-1, IL-6, p<0.05) which is associated to a reduced infiltration of monocytes and macrophages in the tissue as assessed by cell sorting. Of note vascularization was enhanced (increased gene expression of Cd31 and Vegfa in VAT, p<0.05) in VAT from PTX3 KO mice. Sorted VAT macrophages showed enhanced expression of molecules associated with M2-polarization (Arg1, Ym-1, p<0.01). In humans, carriers of the h2/h2 haplotype for PTX3, characterized by lower PTX3 plasma levels compared to h1/h1 carriers, presented with lower BMI and lower abdominal obesity compare to h1/h1 carriers (android fat% h2/h2=45.34±10.32, h1/h1=47.17±9.23, p<0.05). CONCLUSIONS: Our results demonstrate that PTX3 might contribute to the development of obesity by limiting adipose tissue vascularization and promoting macrophage infiltration.
|Titolo:||THE LONG PENTRAXIN 3 PLAYS A KEY ROLE IN THE IMMUNOMODULATION OF DIET-INDUCED OBESITY|
|Supervisori e coordinatori interni:||CATAPANO, ALBERICO LUIGI|
|Data di pubblicazione:||17-dic-2018|
|Parole Chiave:||PTX3; obesity; inflammation|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Citazione:||THE LONG PENTRAXIN 3 PLAYS A KEY ROLE IN THE IMMUNOMODULATION OF DIET-INDUCED OBESITY / A. Moregola ; tutor: G.D. Norata ; coordinatore: A.L. Catapano. - Milano : Università degli studi di Milano. DIPARTIMENTO DI SCIENZE FARMACOLOGICHE E BIOMOLECOLARI, 2018 Dec 17. ((31. ciclo, Anno Accademico 2018.|
|Appare nelle tipologie:||Tesi di dottorato|