Abstract
This study investigated the impacts of GLN on inflammation and T cell dysregulation in obese mice complicated with sepsis. Mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat and was administered for 10 weeks to induce obesity. Mice fed with a high-fat diet were then assigned to sham (SH) and sepsis with saline (SS) or GLN (SG) groups. The SH group was subjected to laparotomy, while the sepsis group underwent cecal ligation and puncture (CLP). The SS group was intravenously injected with saline. The SG group was intravenously administered GLN after CLP. Mice were sacrificed at 12, 24, or 48 h post-CLP, respectively. Results demonstrated that in the presence of obesity, sepsis drove CD4+ T cells toward the helper T (Th)2 and Th17 lineages. Also, expressions of inflammatory cytokines and macrophage infiltration markers in adipose tissues and lungs were elevated. Treatment of obese mice with GLN after sepsis reversed Th polarization and downregulated macrophage infiltration and inflammatory cytokine, whereas the tight junction-associated protein expression increased in the lungs. These findings suggest that the intravenous administration of GLN to obese mice after sepsis modulated a more balanced Th cell lineage, alleviated inflammation, and attenuated lung injury.
Highlights
Obesity is a complex, multifactorial condition that has become an important global health problem
Excessive adipose tissue accumulation was shown to be associated with low-grade inflammation and endothelial dysfunction which may result in cardiovascular diseases, diabetes, stroke, etc
We created a mouse model of obesity complicated with sepsis, because currently, the concomitant presence of obesity and sepsis is an important cause of hospital admissions and mortality in critically ill patients [22, 23]
Summary
Multifactorial condition that has become an important global health problem. Excessive adipose tissue accumulation was shown to be associated with low-grade inflammation and endothelial dysfunction which may result in cardiovascular diseases, diabetes, stroke, etc. Obese subjects were found to have dysregulated innate and adaptive immune responses that may worsen disease outcomes [1, 2]. A previous study showed that obesity is associated with an increased risk of nosocomial and secondary infections that lead to sepsis [3]. Sepsis is a life-threatening syndrome with multiorgan dysfunction [4]. Decline of T lymphocytes and impairment of the T cell function are characteristics of sepsis [5, 6]. The dysregulation of T lymphocytes results in an imbalance between pro- and anti-inflammatory reactions that
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