Glutamine Administration Attenuates Kidney Inflammation in Obese Mice Complicated with Polymicrobial Sepsis.

Li-Han Su,Chiu-Li Yeh,Sung-Ling Yeh,Ming-Tsan Lin,Jie Chen

doi:10.1155/2021/5597118

Li-Han Su, Chiu-Li Yeh + Show 3 more

Open Access

https://doi.org/10.1155/2021/5597118

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Abstract

Obesity is a well-known public health issue around the world. Sepsis is a lethal clinical syndrome that causes multiorgan failure. Obesity may aggravate inflammation in septic patients. Glutamine (GLN) is a nutrient with immune regulatory and anti-inflammatory properties. Since sepsis is a common contributing factor for acute kidney injury (AKI), this study investigated the effects of GLN administration on sepsis-induced inflammation and AKI in obese mice. A high-fat diet which consists of 60% of calories from fat was provided for 10 weeks to induce obesity in the mice. Then, the obese mice were subdivided into sepsis with saline (SS) or GLN (SG) groups. Cecal ligation and puncture (CLP) was performed to produce sepsis. The SS group was intravenously injected with saline while the SG group was administered GLN one or two doses after CLP. Obese mice with sepsis were sacrificed at 12, 24, or 48 h post-CLP. Results revealed that sepsis resulted in upregulated high-mobility group box protein-1 pathway-associated gene expression in obese mice. Also, expressions of macrophage/neutrophil infiltration markers and inflammatory cytokines in kidneys were elevated. Obese mice treated with GLN after sepsis reversed the depletion of plasma GLN, reduced production of lipid peroxides, and downregulated macrophage/neutrophil infiltration and the inflammatory-associated pathway whereas tight junction gene expression increased in the kidneys. These findings suggest that intravenously administered GLN to obese mice after sepsis alleviated inflammation and attenuated AKI. This model may have clinical application to obese patients with a risk for infection in abdominal surgery.

Highlights

Obesity is an important public health issue worldwide because of its high global prevalence
NGAL levels in the SG group were significantly lower at 24 h and KC were lower at 12 h than those in the sepsis with saline (SS) group post-cecal ligation and puncture (CLP) (Table 3)
There are increasing numbers of obese patients being admitted to intensive care unit (ICU) [24]

Summary

Introduction

Obesity is an important public health issue worldwide because of its high global prevalence. Obesity is mainly caused by high calorie intake and deficiency of physical activity that develop gradually with cellular physiologic changes before the symptoms of diseases become apparent. Obesity results in dysregulation of immune responses [1]. These changes are closely associated with metabolic disturbances that may have adverse impact on host immunity during infection and promote disease progression [1, 2]. Obese subjects are considered frail with increased risk of recurrent nosocomial infections [2]. In the critically ill population, a previous study found that compared to normal weight, obese patients have higher risk of infectious complications that lead to sepsis [3]

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