Interleukin 33 contributes to vascular functional changes mediated by the perivascular adipose tissue in mice submitted to high-fat diet

Author(s)

Rafael Menezes da Costa

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2018-01-26

Examining board members

Rita de Cassia Aleixo Tostes Passaglia; Thiago Mattar Cunha; Daniela Carlos Sartori

• Advisor: Rita de Cassia Aleixo Tostes Passaglia

Abstract

Obesity triggers functional changes in the perivascular adipose tissue (PVAT), favoring the release of vasoconstrictor factors. Interleukin-33 (IL-33) signaling, via ST2 receptor, is essential for the development and maintenance of regulatory T cells (Tregs) in the visceral adipose tissue. In obesity, Tregs function is compromised, resulting in adipose tissue inflammation. We hypothesized that high fat diet (HFD) decreases the number and function of Tregs and increases inflammation in the PVAT. Mice deficient for the ST2 receptor (ST2 KO) and their respective controls (Balb/C mice) were fed a control diet or a HFD for 18 weeks. Vascular function was evaluated in mesenteric resistance arteries, by performing concentration-effect curves to phenylephrine (PE). In Balb/C mice fed the control diet, PVAT decreased vascular PE contractions. However, a partial loss of PVAT anticontractile effect occurred in arteries from HFD-fed Balb/C mice. In arteries from ST2 KO mice fed the control diet, PVAT decreased PE contractions. However, a complete loss of PVAT anticontractile effects was observed in HFD-fed ST2 KO mice. There was a decrease in the number of Tregs and an increase in the number of neutrophils in the PVAT of mice fed the HFD. The absence of the IL-33 receptor increased IL-6 and reduced IL-10 in HFD-fed mice. There was an increase in superoxide anion levels in the PVAT of Balb/C mice fed HFD and the absence of the ST2 receptor potentiated this effect. These data show that HFD promotes PVAT dysfunction and IL-33 is fundamental to counteract HFD-induced PVAT dysfunction. (AU)

• FAPESP's process: 16/14078-0 - Interleukin 33 contribution in vascular changes mediated by perivascular adipose tissue in mice submitted to high-fat diet
• Grantee: Rafael Menezes da Costa
• Support Opportunities: Scholarships in Brazil - Doctorate