Role for BLT1 in adipose tissue inflammation in old mice

Abstract

Aging is a complex biological process characterized by obesity and immunosenescence. Immunosenescence indicates the decline in immune function and the increase in chronic-low grade inflammation, called "Inflammaging". Adipose tissue accumulation, particularly visceral adipose tissue (VAT), is associated with an increase in pro-inflammatory macrophages that play an important role in modulating immune responses and producing inflammatory cytokines. The leukotriene B4 receptor 1 (BLT1) is a regulator of obesity-induced inflammation. Its ligand, LTB4, acts as a chemoattractant for immune cells and induces inflammation. Studies showed that BLT1 is crucial for cytokine production during lipopolysaccharide infection of young mice. However, the expression patterns and function of BLT1 in the adipose tissue of older organisms remains unknown. In this study, we investigated BLT1 expression in immune cell subsets within the VAT of aged male and female mice. Moreover, we examined how BLT1 expression alters in response to lipopolysaccharide, in the aging context. Our results demonstrate that aged mice exhibit increased obesity and inflammation, characterized by elevated frequencies of B and T cells, along with pro-inflammatory macrophages in VAT. BLT1 expression is the highest in VAT macrophages and BLT1 showed an increased expression in pro-inflammatory macrophages from aged mice. An in vitro model of bone marrow derived macrophages supported these in vivo findings. Treatment of aged mice with BLT1 antagonist, U75302, followed by lipopolysaccharide-induced endotoxemia resulted in a reduction in pro-inflammatory macrophages and an increase in anti-inflammatory macrophages. This study provides valuable insights into the age-specific changes in BLT1 expression and its impact on immune cell subsets within VAT. This study offers support for its potential for modulating inflammation in aging.