Abstract

Obesity is a health problem associated with many metabolic disorders. Weight reduction can effectively alleviate obesity-associated complications. Sleeve gastrectomy is a commonly used bariatric surgery and is considered safe and effective for improving outcomes. Glutamine (GLN) is an amino acid with anti-oxidative and anti-inflammatory properties. This study used a mouse model of sleeve gastrectomy to investigate the impacts of intravenous GLN administration on glucose tolerance and adipocyte inflammation short-term after surgery. C57BL6 male mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat for 10 weeks to induce obesity. Mice fed the high-fat diet were then assigned to a sham (SH) or sleeve gastrectomy with saline (S) or GLN (G) groups. The S group was intravenously injected with saline, while the G group was administered GLN (0.75 g/kg body weight) via a tail vein postoperatively. Mice in the experimental groups were sacrificed on day 1 or 3 after the surgery. Results showed that obesity resulted in fat accumulation, elevated glucose levels, and adipokines production. Sleeve gastrectomy aggravated expressions of inflammatory cytokine and macrophage infiltration markers, cluster of differentiation 68 (CD68), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR-1), and macrophage chemoattractant protein-1, in adipose tissues. Treatment of obese mice with GLN downregulated hepatic proteomic profiles associated with the gluconeogenesis pathway and improved glucose tolerance. Moreover, macrophage infiltration and adipose tissue inflammation were attenuated after the sleeve gastrectomy. These findings imply that postoperative intravenous GLN administration may improve glucose tolerance and attenuate inflammation shortly after the bariatric surgery in subjects with obesity.

Highlights

  • Obesity is an important public health issue worldwide

  • Excessive fat mass accumulation and adipose tissue inflammation are positively correlated with insulin resistance (IR), glucose intolerance, and other associated metabolic dysfunctions [2]

  • We found that diet-induced obesity (DIO) mice intravenously administered GLN after sleeve gastrectomy exhibited several favorable effects that were not observed in the saline groups

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Summary

Introduction

Obesity is an important public health issue worldwide. According to a report from three consecutive waves of the Nutrition and Health Surveys in Taiwan (NAHSIT), prevalence of morbid obesity and obesity increased sharply from 1993–1996 and 2013–2014 [1]. Obesity is a condition of low-grade systemic inflammation. Immune cells infiltrate into enlarged adipocytes leading to persistent proinflammatory mediator production, which is considered the sole mechanism [2]. Excessive fat mass accumulation and adipose tissue inflammation are positively correlated with insulin resistance (IR), glucose intolerance, and other associated metabolic dysfunctions [2]. Epidemiological studies showed that obesity is associated with increased risks of many metabolic disorders, such as cardiovascular diseases, hypertension, type 2 diabetes, stroke, etc. [3], and mortality is increased [4]. Weight reduction can effectively alleviate multiple obesity-related complications [5]

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